ENDOCRINOLOGY
Location of major endocrine glands
By US Government - Derived from File:Illu_endocrine_system.jpg, itself from http://training.seer.cancer.gov/module_anatomy/unit6_3_endo_glnds.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=15860440
ADRENAL GLANDS:
EMBRYOLOGY:
· The CORTEX forms as a result of 2 episodes of mesoderm proliferation.
o 1st episode: forms the fetal cortex, which regresses by the 2nd postnatal month
o 2nd episode: forms the adult cortex (i.e. the GFR)
· The MEDULLA forms from neural crest cells, which migrate to the fetal cortex and differentiate into chromaffin cells.
ANATOMY: Situated atop the kidneys, specifically on their anterosuperior aspect, at the level of the 12th thoracic vertebra. The right gland is lateroposterior to the IVC and medial to the liver. The left gland is inferior to the stomach and above the pancreas.
· Blood supply from the adrenal arteries:
o The superior suprarenal artery is provided by the inferior phrenic
o The middle suprarenal artery is provided by the abdominal aorta
o The inferior suprarenal artery is provided by the renal artery
· Venous drainage via the suprarenal veins:
o The right suprarenal vein drains into the IVC
o The left suprarenal vein drains into the left renal vein or the left inferior phrenic vein.
o The suprarenal veins receive blood may form anastomoses with the inferior phrenic veins.
· The adrenal gland is separated into two distinct structures, both of which receive regulatory input from the nervous system: Cortex & Medulla
Adrenal gland
By EEOC - cancer.gov, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1394171
ADRENAL GLANDS:
EMBRYOLOGY:
ANATOMY:
BASIC ADRENAL HISTOLOGY:
PATHOLOGY: CAP (it looks like a cap on the kidney) --> CAH (congenital adrenal hyperplasia), Cushing’s syndrome, Conn’s syndrome, Addison’s disease (Adrenal insufficiency), Pheochromocytoma.
· C _______________, _______________, _______________, _______________, _______________
· A _______________, _______________, _______________, _______________, _______________
P _______________, _______________, _______________, _______________, ________________
PANCREAS
EMBRYOLOGY:
ANATOMY:
BASIC PANCREATIC HISTOLOGY:
PANCREATIC ENDOCRINE DISEASES: Diabetes Mellitus; ISLET CELL TUMORS: GIVES --> G-gastrinoma, G-glucagonoma, I-insulinoma, V-VIPoma, E-Everything else (PPoma, & others), S-somatostatinoma;
· Diabetes Mellitus
· ISLET CELL TUMORS: GIVES --> G astrinoma, G lucagonoma, I nsulinoma, V IPoma, E verything else (PPoma, & others), S omatostatinoma.
o G _______________, _______________, _______________, _______________, _______________
o I _______________, _______________, _______________, _______________, _______________
o V _______________, _______________, _______________, _______________, ________________
o E _______________, _______________, _______________, _______________, _______________
o S _______________, _______________, _______________, _______________, _______________
PARATHYROID GLANDS:
EMBRYOLOGY:
ANATOMY:
BASIC PARATHYROID HISTOLOGY:
PARATHYROID DISEASES: Hyperparathyroidism; Hypoparathyroidism; Pseudohypoparathyroidism;
PITUITARY GLAND
§ EMBRYOLOGY:
§ ANATOMY:
§ BASIC PITUITARY HISTOLOGY:
· PITUITARY DISEASES:
o Classification: Oversecretion versus Undersecretion of hormones
Ø Oversecretion: Occur with pituitary adenoma (SEE TABLE BELOW)
Ø Undersecretion: Panhypopituitarism (↓ all anterior hormones). Diabetes insipidus (↓ ADH)
THYROID GLAND
§ EMBRYOLOGY:
§ ANATOMY:
§ BASIC PITUITARY HISTOLOGY:
THYROID DISEASES: HYPERTHYROIDISM; GRAVE’S DISEASE; HYPOTHYROIDISM (MYXEDEMA, CRETINISM);
Ø THYROID DISEASES: THYROIDITIS (Major types: Hard Dick Requires Puss’--> HDRP --> Hashimoto’s, De Quervain’s, Reidel’s, and Postpartum thyroiditis); THYROID NODULES; THYROID TUMORS (Benign: THYROID ADENOMA, Malignant: Papa Feverishly Hump Mama’s Asrse = PFHMA --> Papillary cancer, Follicular cancer, Hurthle cell variant, Medullary cancer, Anaplastic cancer.
ENDOCRINOLOGIC SYNDROMES: MULTIPLE ENDOCRINE NEOPLASIA:
Section of human adrenal gland under the microscope, showing its different layers. From the surface to the center: zona glomerulosa, zona fasciculata, zona reticularis, medulla. In the medulla, the central adrenomedullary vein is visible.
By Jpogi - https://commons.wikimedia.org/wiki/File:Adrenal_gland_%28cortex%29.JPG, CC0, https://commons.wikimedia.org/w/index.php?curid=37838551
Cortex: devoted to the synthesis of corticosteroid hormones from cholesterol. 3 zones
Stimulated by
Renin-Angiotensin
ACTH
ACTH
Various stressors
Mnemonic that is used is Go Find Rex, Make Good Sex: G - glomerulosa, F - fasciculata, R - reticularis, M - mineralcorticoids, G - glucocorticoids, S - sex hormones.
o Medulla: Composed of hormone-producing chromaffin cells. In particular, they are modified postganglionic cells of the sympathetic nervous system that have lost their axons and dendrites, receiving innervation from corresponding preganglionic fibers. It is the principal site of the conversion of the amino acid tyrosine into the catecholamines norepinephrine, epinephrine, and dopamine.
Ø #1 adrenal tumor in adult is pheochromocytoma; in children is neuroblastoma
Steroidogenesis in the adrenal glands – different steps occur in different layers of the gland
By Copyright © 2014 Matthew Colo, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=31105570
ADRENAL GLANDS DISEASE: CAP (it looks like a cap on the kidney) --> CAH (congenital adrenal hyperplasia), Cushing’s syndrome, Conn’s syndrome, Addison’s disease (Adrenal insufficiency), Pheochromocytoma.
· C _______________, _______________, _______________, _______________, _______________
· A _______________, _______________, _______________, _______________, _______________
· P _______________, _______________, _______________, _______________, ________________
· C AH (congenital adrenal hyperplasia): several autosomal recessive diseases resulting from defects in steps of the steroidogenesis of cortisol from cholesterol by the adrenal glands. Most of these diseases involve excessive or deficient production of sex steroids and can pervert or impair development of primary or secondary sex characteristics in affected infants, children, and adults.
Summary of CAH: CAH -->
CAH --> Cortisol & Aldosterone deficiency due to 3, 11, 17, 21b-Hydroxylase deficiency
CAH --> Child Ambiguous genital (♀) or Hypertrophy of the genital (♂)
Ø C ortisol deficiency --> Hypoglycemia, A ldosterone deficiency à Adrenal crisis with salt-wasting (treat with Fludricortisone), HTN with 11, 17b-Hydroxylase deficiency.
Ø C ortisol deficiency --> A CTH ↑ --> Androgen ↑
Ø Treatment: C ortisol to ↓ ACTH --> ↓ Androgen.
C _______________, _______________, _______________, _______________, _______________
A _______________, _______________, _______________, _______________, _______________
H _______________, _______________, _______________, _______________, ________________
C _______________, _______________, _______________, _______________, _______________
A _______________, _______________, _______________, _______________, _______________
H _______________, _______________, _______________, _______________, ________________
Treatment: of all forms of CAH may include any of: 1) supplying enough glucocorticoid to reduce hyperplasia and overproduction of androgens or mineralocorticoids 2) providing replacement mineralocorticoid and extra salt if the person is deficient 3) providing replacement testosterone or estrogen at puberty if the person is deficient 4) additional treatments to optimize growth by delaying puberty or delaying bone maturation 5) genital reconstructive surgery to correct problems produced by abnormal genital structure
Negative feedback in the HPA axis
By DRosenbach - http://en.wikipedia.org/wiki/File:ACTH_Negative_Feedback.jpgmade by en:User:DRosenbachhttp://en.wikipedia.org/wiki/File:ACTH_Negative_Feedback.svgSVGized by en:User:XRDoDRX, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=8018236
· C ushing’s Syndrome: High levels of cortisol in the blood.
Types:
Ø ↑ ACTH: 1) Cushing’s disease (primary pituitary adenoma) 2) Ectopic ACTH (SCC of lung)
Ø ↓ ACTH: 1) Primary adrenal hyperplasia 2) Iatrogenic (#1): ↓ DHEA (↑ in all others types)
Evaluation: CORTISOL --> Cow’s hump, Obese, Osteoporosis, Red Round face, Truncal obesity, Insulin resistance, Immunosuppression, Striae, Skin thin, Oligomenorrhea, Low LH/FSH.
Ø C _______________, _______________, _______________, _______________, _______________
Ø O _______________, _______________, _______________, _______________, _______________
Ø R _______________, _______________, _______________, _______________, ________________
Ø T _______________, _______________, _______________, _______________, _______________
Ø I _______________, _______________, _______________, _______________, _______________
Ø S _______________, _______________, _______________, _______________, ________________
Ø O _______________, _______________, _______________, _______________, _______________
Ø L _______________, _______________, _______________, _______________, ________________
Screen: low dose dexamethason suppression test fails to suprress cortisol to < 5 mg/dL. Confirm: 24 hr free urine cortisol > 300 mg. Differentiate: High dose dexamethasone suppress only ACTH-secreting pituitary adenoma. CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of an adrenal or pituitary adenoma.
Treatment: an adrenal adenoma is identified it may be removed by surgery. Pituitary ACTH producing adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients will require steroid replacement postoperatively at least in the interim as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. In those patients not suitable for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy. Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation. This clinical situation is known as Nelson's syndrome. In iatrogenic Cushing's, dose adjustment may be sufficient or it may be necessary to change to another type of immunosuppresive medication.
Increased hair and stria in a person with medication-induced Cushing’s syndrome
By Ozlem Celik, Mutlu Niyazoglu, Hikmet Soylu and Pinar Kadioglu - http://mrmjournal.biomedcentral.com/articles/10.1186/2049-6958-7-26, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=47877334
Features of Cushing syndrome including a round face, acne, reddish skin, central obesity, and poor muscle tone
By Elizabeth B. Fudge,1 Daniel von Allmen,2 Keith E. Volmar,3 and Ali S. Calikoglu1 - (2009). "Cushing Syndrome in a 6-Month-Old Infant due to Adrenocortical Tumor". International Journal of Pediatric Endocrinology 2009: 1–4. DOI:10.1155/2009/168749. ISSN 1687-9848., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=47877602
· C onn’s Syndrome (primary hyperaldosteronism): #1 due to ↑ aldosterone from unilateral adrenal adenoma; most remaining from bilateral adrenocortical hyperplasia.
Evaluation: HTN/HA/tetany/paresthesia (due to hyperNa+), polyurria/muscle weakness (due to hypoK+ nephropathy), low serum renin. 24hr urine aldosterone ↑. CT/MRI (look for adrenal mass), metabolic alkalosis.
Treatment: Adrenalectomy: for adrenal adenoma. Spironolactone or amiloride (choice for ♂): for bilateral adrenal hyperplasia, for which adrenalectomy provides no benefit.
Secondary hyperaldosteronism (↑ renin): RAS (renal artery stenosis), RF, CHF, cirrhosis.
· A drenal Insufficiency:
Primary (Addison’s disease): Deficient both mineralocorticoids and glucocorticoids secondary to the destruction of the adrenal cortices.
Ø Etiologies:
Ø Autoimmune (#1): may be a part of Polyglandular Autoimmune Syndrome = Ph.D VT --> PCOS (polycystic ovarian syndrome), Hashimoto thyroiditis, DM type I, Vitiligo, Testicular atrophy
§ P _______________, _______________, _______________, _______________, _______________
§ H _______________, _______________, _______________, _______________, _______________
§ D _______________, _______________, _______________, _______________, ________________
§ V _______________, _______________, _______________, _______________, _______________
§ T _______________, _______________, _______________, _______________, _______________
v Infection (#2): Tb, histoplasmosis
v Waterhouse-Friderichsen syndrome: Adrenal hemorrhagic necrosis due to meningococcemia.
Ø Evaluation: Weakness, weight loss, N/V, abdominal pain, hypotension, hypoNa+, hyperK+, ↑ BUN
v Addison’s crisis: hypoglycemia, N/V --> dehydration, cardiovascular collapse), skin hyperpigmentation (secondary to ↑ ACTH). CBC: eosinophilia.
Ø Treatment: Prednison & Fludrocortisone
Secondary: Most secondary to abrupt stop of cortisol therapy leaving the patient in a state of ↓ ACTH. NO hyperK+ & hypoNa+ because the RAAS still intact
Characteristic skin hyperpigmentation in Addison's disease
By http://wellcomeimages.org/indexplus/obf_images/8f/3b/1b12bb2524c61338b34822f8ef7b.jpgGallery: http://wellcomeimages.org/indexplus/image/L0018484.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=35985120
Classic hyperpigmentation of Addison's disease
By FlatOut - Dermatology Online Journal http://dermatology.cdlib.org/, CC0, https://commons.wikimedia.org/w/index.php?curid=25847348
· P hechromocytoma (#1 adrenal tumor in adults): Tumor of the chromaffin cell --> ↑ NE/EPI. Associated with VHL, MEN, NF. Important cause of surgically correctable HTN
Evaluation: Intermittent hyperadrenergic 5 P’s --> P ressure of blood (↑ BP), P ain (HA), P erspiration, P alpitation, P allor
Ø P _______________, _______________, _______________, _______________, _______________
Ø P _______________, _______________, _______________, _______________, _______________
Ø P _______________, _______________, _______________, _______________, ________________
Ø P _______________, _______________, _______________, _______________, _______________
Ø P _______________, _______________, _______________, _______________, _______________
Rule of 10% --> 10% occur in children, 10% bilateral, 10% malignant, 10% calcified, 10% familial, 10% extra-adrenal (these are called Paraganlioma). 24 hour metanephrines, VMA, HVA. CT/MRI: supra-adrenal mass.
Treatment: a-antagonist (phentolamine, phenoxybenzamine) first --> then bB (propanolol) --> surgery. Post-op: check urine metanephrines for recurrence
Neuroblastoma (#1 adrenal tumor in kid): Characteristic amplification of N-myc gene 1000’s copies on chromosome 1. N-Myc Gene = NMG --> tumor secreting excessive NE/EPI --> HTN, tumor presents as Mass in the abdomen, tumor can spontaneously transform into a Ganglioneuroma (a more differentiated form); Malignant form can differentiate into a more benign form w/ ↓ NMG gene amplification.
Ø N _______________, _______________, _______________, _______________, _______________
Ø M _______________, _______________, _______________, _______________, _______________
Ø G _______________, _______________, _______________, _______________, ________________
Pheochromocytoma (dark circular shadow near body center) localized by MIBG scintigraphy. Front and back views also show radioiodine collection in thyroid (neck) and bladder (pelvis)
By Drahreg01 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=10586988
Pheochromocytoma. CT abdomen.
By Unknown - http://www.cc.nih.gov/ccc/papers/vonhip/adrenal.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=5622670
Micrograph of a pheochromocytoma (at high magnification) showing the characteristic stippled (finely granular) chromatin. The chromatin pattern is sometimes referred to as "salt-and-pepper" chromatin.
By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5938524
PANCREAS
EMBRYOLOGY
Pancreas arises from 2 separate outpouchings of the primordial foregut
• Ventral bud & its duct from hepatic endoderm
• Dorsal bud & its duct from duodenal endoderm
Around the 6th week, the ventral bud migrates dorsally in a clockwise fashion and fuse with the dorsal bud.
• Ventral bud à Uncinate process & superior pancreatic head
• Dorsal bud à Inferior head, neck, body, & tail
Duct systems of the 2 pancreatic buds fuse as well
• In > 90% of individuals, the proximal 1/3 of the dorsal pancreatic duct regresses as it fuses with the ventral duct à main pancreatic duct (Wirsung) à drain to Ampulla of Vater of duodenum
Annular pancreas: when the ventral bud rotates incorrectly resulting around the duodenum --> obstructing it.
Schematic illustrating the development of the pancreas from a dorsal and a ventral bud. During maturation, the ventral bud flips to the other side of the gut tube (arrow) where it typically fuses with the dorsal lobe. An additional ventral lobe that usually regresses during development is omitted.
Pancreas of a human embryo at end of sixth week
By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 1102, Public Domain, https://commons.wikimedia.org/w/index.php?curid=567063
ANATOMY
• Retroperitoneal organ. Lies posterior to the stomach and anterior to the IVC & aorta.
• Head – in C of duodenum, anterior to IVC, SMA & SMV
• Uncinate process – posterior to SMA & SMV
• Body – anterior to aorta, left adrenal and kidney
• Tail – in splenic hilum
Blood supply:
• Gastroduodenal artery --> Superior Pancreaticoduodenal artery.
• SMA --> Inferior Pancreaticoduodenal artery
o Both --> Anterior & Posterior Pancreaticoduodenal arteries to supply the head, neck & uncinate process
• Splenic artery --> Left gastro-omental artery that supplies body and tail
Innervation:
• Sympathetic (celiac plexus splanchnics): transmit pain signal
• Parasympathetic (celiac division of vagus): Islet, acini, ductal cells
Pancreatic tissue, including a pancreatic islet
By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=28909220
The duodenum and pancreas
By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 1098, Public Domain, https://commons.wikimedia.org/w/index.php?curid=567057
Duodenum and pancreas. Deep dissection.
By Anatomist90 - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=50266118
EXOCRINE PANCREAS
80% of pancreatic mass. Composed of discrete subunits called “ACINI”.
o Acini: 20-50 acinar cells spherically distributed forming an alveolus. Acinar cells produce digestive enzymes. All enzymes are produced in inactive form (proenzymes) EXCEPT Lipase, Amylase, Nuclease. PREVENT AUTODIGESTION! Acinar cells are stimulated by CCK (↑ in duodenum in response to FA, AA, Oligopeptides)
o Intercalated duct cells secrete HCO3- (pH 7-8). These cells are stimulated by secretin (↑ by HCl in upper small bowel)
o Pancreatic proenzymes are activated (eg. Trysinogen --> Trypsin) by duodenal Enterokinase. Trypsin then activates itself and other pancreatic enzymes
PHYSIOLOGY:
ENDOCRINE PANCREAS
The islets of Langerhans --> 20% of pancreatic mass
· A-alpha-cell --> Glucagon --> liver gluconeogenesis, glycogenolysis, and lipolysis (via the promotion of carnitine-mediated FA transport into the mitochondria).
· B-beta-cell --> Insulin --> promote glycogen synthesis, triglyceride storage
· D-delta-cell --> SST (somatostatin) --> inhibit glucagon and insulin secretion and slow digestive function
Pancreatic islets, the lighter tissue among the darker, acinar pancreatic tissue, hemalum-eosin stain.
By User:Polarlys - Own work, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=1032935
PANCREATIC ENDOCRINE DISEASES
· Diabetes Mellitus: a metabolic disorder characterized by hyperglycemia. Leading cause of ESRD (end stage renal disease) and blindness worldwide.
2 major types:
Ø Type I (aka IDDM or juvenile diabetes): Autoimmune destruction of the b-cells à insulin deficiency. Associated with HLA-DR3 & 4.
Ø Type II (aka NIDDM or adult-onset diabetes): Peripheral tissue insulin-resistance.
Evaluations: Classic symptoms of diabetes 3’P --> Polyphagia, Polydipsia, Polyuria, and rapid weight loss. DM is diagnosed by 1 of the following 3 is met:
1. Fasting Blood Sugar > 126 mg/dL on ≥ 2 separate occasions
2. Random Blood Sugar > 200 mg/dL with classical symptoms of diabetes
3. 2 hours Postprandial > 200 mg/dL (normal <140) on ≥ 2 separate occasions
UA (glucoses, ketones, protein), HbA1c (goal < 7), CBC, CMP, FLP, Microalbuminuria (30-300 mg/24hr), Dilated eye exam (retinopathy usually precedes nephropathy). Drugs causing hyperglycemia: STOP --> Steroids, Thiazide, OCP, Phenytoin, Pentamidine, Protease inhibitors, Propanolol (& other beta-blockers)
Ø S _______________, _______________, _______________, _______________, _______________
Ø T _______________, _______________, _______________, _______________, _______________
Ø O _______________, _______________, _______________, _______________, ________________
Ø P _______________, _______________, _______________, _______________, _______________
Overview of the most significant symptoms of diabetes
By Mikael Häggström - See above. All used images are in public domain., Public Domain, https://commons.wikimedia.org/w/index.php?curid=6055528
The fluctuation of blood sugar (red) and the sugar-lowering hormone insulin (blue) in humans during the course of a day with three meals — one of the effects of a sugar-rich vs a starch-rich meal is highlighted.
By Jakob Suckale, Michele Solimena - Solimena Lab and Review Suckale Solimena 2008 Frontiers in Bioscience PMID 18508724, preprint PDF from Nature Precedings, original data: Daly et al. 1998 PMID 9625092, CC BY 3.0, https://en.wikipedia.org/w/index.php?curid=24016521
Mechanism of insulin release in normal pancreatic beta cells — insulin production is more or less constant within the beta cells. Its release is triggered by food, chiefly food containing absorbable glucose.
By Fred the OysteriThe source code of this SVG is valid.This vector graphics image was created with Adobe Illustrator., GFDL, https://commons.wikimedia.org/w/index.php?curid=36631663
Treatment: HTN (ACEI [especially for DM type I], ARB [especially for DM type II]; second line CCB [verapamil, diltiazem]): target BP 135/80. HLP (hyperlipidemia): target LDL < 70. Oral hypoglycemics or Insulins.
Ø PO Hypoglycemics: SIGMA --> S ulfonylurea (eg, glypizide, ↑ insulin secretion, (-): weight gain & hypoglycemia), S itagliptin (DPP4-inhibitor [dipeptidyl peptidase-4] works by inhibiting the inactivation of the incretin GLP-1 & GIP by DPP4), I ncretin (eg, Exenatide an insulin secretagogue with glucoregulatory effects, (-): N/V), G litazone (aka thiazolidinediones, eg, rosiglitazone, ↓ peripheral insulin-resistance, (-): hepatotoxic, weight gain), M etformin (one of the biguanides, ↓ gluconeogenesis, (-): avoid in CHF, renal disease [Cr > 1.5], & liver disease because ↑ of lactic acidosis), M eglitinide (eg, repaglinide block K+ channel in b cells --> closes the ATP-dependent K+ channels and opens the cells' Ca++ channels --> cells to secrete insulin, short-acting à give with meals), A lpha-glucosidase inhibitor (eg, acarbose).
v S _______________, _______________, _______________, _______________, _______________
v I _______________, _______________, _______________, _______________, _______________
v G _______________, _______________, _______________, _______________, ________________
v M _______________, _______________, _______________, _______________, _______________
v A _______________, _______________, _______________, _______________, _______________
Ø Insulins: AL Regulates Nasty Glucose (in order of increasing ½ life) = AL (short acting) RN (intermediate) G (long-acting) --> Aspart, Lispro, Regular, NPH, Glargine (lantus)
v A _______________, _______________, _______________, _______________, _______________
v L _______________, _______________, _______________, _______________, _______________
v R _______________, _______________, _______________, _______________, ________________
v N _______________, _______________, _______________, _______________, _______________
G _______________, _______________, _______________, _______________, _______________
Complications:
Ø Acute Complications:
v DKA (diabetic ketoacidosis): hyperglycemic crisis occurring mostly in DM type I precipitated by stress, infections, MI, EtOH, drugs (STOP), or insulin noncompliance.
§ Evaluation: DKA --> D ehydration, K ussmaul respiration (rapid, deep breaths), K+ ↓ (secondary to osmotic diuresis), K etone bodies ↑, A bdominal pain, A ltered mental status, A nion gap metabolic Acidosis, Afebrile.
o D _______________, _______________, _______________, _______________, _______________
o K _______________, _______________, _______________, _______________, _______________
o A _______________, _______________, _______________, _______________, ________________
§ Treatment: IVF, IV insulin (bolus 10 U followed by continuous 0.1 U/kg/hr), K+
v HNS (hyperosmolar nonketotic state AKA HHNK coma-hyperosmolar hyperglycemic nonketotic): Usually precipitated by an acute illness, MI or stroke. A relative insulin deficiency leads to a serum glucose that is usually > 600 mg/dl, and a resulting serum osmolarity > 350 mOsm. This leads to polyuria (an osmotic diuresis), which, in turn, leads to volume depletion and hemoconcentration that causes a further increase in blood glucose level. Ketosis is absent because the presence of some insulin inhibits lipolysis, unlike diabetic ketoacidosis. Untreated 50% mortality.
§ Evaluation: HNS --> H yperviscosity (↑ thrombosis), N eurologic signs (confusion, flaccidity, depressed reflexes, tremors), S eizures
o H _______________, _______________, _______________, _______________, _______________
o N _______________, _______________, _______________, _______________, _______________
o S _______________, _______________, _______________, _______________, ________________
§ Treatment: IVF, E-lytes, IV insulin, LMWH
β-hydroxybutyrate, despite chemically containing a carboxylic acid instead of a ketone, is the principal "ketone body" in diabetic ketoacidosis.
By Fvasconcellos - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=8119026
Dehydration may be severe in diabetic ketoacidosis, and intravenous fluids are usually needed as part of its treatment
By Harmid - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4657586
Ø Chronic Complications:
§ Microvascular disease: Retinopathy, Nephropathy, Neuropathy
o Retinopathy: 1) Non-proliferative Diabetic Retinopathy: microaneurysm, soft (ischemic injury) and hard exudates (vascular leakage) 2) Proliferative Diabetic Retinopathy: overcompensation for ischemic retina --> neovascularization --> hemorrhage.
Ø Evaluation: blurred vision. Annual visual acuity test, opthalmoscopic exam, tonometry.
Ø Treatment: control blood sugar, HTN. Laser photocoagulation for retinal neovascularization.
Illustration depicting diabetic retinopathy
By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27924386
Normal vision
By National Eye Institute, National Institutes of Health - http://www.nei.nih.gov/photo/keyword.asp?narrow=Eye+Disease+Simulation&match=all (TIFF image), Public Domain, https://commons.wikimedia.org/w/index.php?curid=10172424
The same view with diabetic retinopathy.
By National Eye Institute, National Institutes of Health - http://www.nei.nih.gov/photo/keyword.asp?narrow=Eye+Disease+Simulation&match=all (TIFF image), Public Domain, https://commons.wikimedia.org/w/index.php?curid=10172592
o Nephropathy (a type of nephrotic syndrome): ↑ mesangial deposit --> 1) Diffuse hyalinization or 2) Nodular glomerulosclerosis (Kimmelstiel-Wilson syndrome).
Ø Evaluation: Symptoms of nephrotic syndrome. UA (microalbuminuria-proteinuria). Biopsy.
Ø Treatment: control blood sugar, HTN (ACEI or ARB). Dialysis. Renal transplant.
Nodular glomerulosclerosis
Public Domain, https://commons.wikimedia.org/w/index.php?curid=2740312
o Neuropathy: result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum). Relatively common conditions associated with diabetic neuropathy include third nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy.
Ø Evaluation: orthostasis, incontinence of urine/stool, sensory pain, delayed gastric emptying, esophageal dysmotility, & impotence.
Ø Treatment: TCA (amitriptyline-Elavil), SSRIs (fluoxetin-Prozac), SNRIs (duloxetin-Cymbalta --> FDA approved for DM neuropathy), anti-convulsant (gabapentin-Neurontin).
Illustration depicting areas affected by diabetic neuropathy
By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27924387
§ Macrovascular disease: Cardiovascular (#1 death in diabetics), Cerebrovascular, Peripheral vascular disease. Treatment: ASA 81 mg. BP <135/80. LDL <70 mg/dL. TG <150 mg/dL
· ISLET CELL TUMORS: GIVES --> G astrinoma, G lucagonoma, I nsulinoma, V IPoma, E verything else (PPoma, & others), S omatostatinoma.
o G _______________, _______________, _______________, _______________, _______________
o I _______________, _______________, _______________, _______________, _______________
o V _______________, _______________, _______________, _______________, ________________
o E _______________, _______________, _______________, _______________, _______________
o S _______________, _______________, _______________, _______________, _______________
Pancreatic insulinoma
CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=507384
PARATHYROID GLANDS:
· EMBRYOLOGY:
- The parathyroid glands originate from the interaction of neural crest mesenchyme and third and fourth pharyngeal pouch endoderm.
- Superior parathyroid glands arise from the 4th branchial pouch.
- Inferior parathyroid glands arise from the dorsal 3rd branchial pouch
The four circles represent the most common position of the parathyroid glands, which are generally four in number and situated behind the lateral lobes of the thyroid gland
Public Domain, https://commons.wikimedia.org/w/index.php?curid=378944
· ANATOMY: Parathyroid glands are usually located behind the thyroid gland. Most often there are four parathyroid glands, but some people have six or even eight. The pair superior parathyroid glands lie in close association with the inferior thyroid artery. The 2 lower glands are usually located within 2 cm of the lower thyroid pole.
o Arterial supply: Inferior thyroid artery from the thyrocervical trunk.
Scheme showing development of branchial epithelial bodies. I, II, III, IV.
By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 1175, Public Domain, https://commons.wikimedia.org/w/index.php?curid=567157
The small, dark cells are chief cells, which are responsible for secreting parathyroid hormone. The cells with orange/pink staining cytoplasm are oxyphil cells.
By original by Nephroncropped by Snowmanradio - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=33269179
· PHYSIOLOGY: The sole function of the parathyroid glands is to maintain the body's calcium level within a very narrow range, so that the nervous and muscular systems can function properly.
o CaSR: transmembrane Ca++ Sensing Receptor in parathyroid chief cells. The signal transduction pathway is activated depends on the # of Ca++ binding sites on the receptor occupied by Ca++.
Ø High serum [Ca++]: saturation of Ca++ binding sites --> activate PLC --> ↑ IP3/DAG --> ↓ PTH release
Ø Low serum [Ca++]: activate AC --> ↑ cAMP --> ↑ PTH release
o PTH function: ↑ serum free Ca++, ↓ serum PO4-, ↑ urine PO4- via these action
Ø ↑ Ca++ resorption from bone secondary to the stimulation of both osteoclasts & osteoblasts
Ø ↑ kidney reabsorption of Ca++
Ø ↑ kidney excretion of PO4-
Ø ↑ kidney conversion of of Vit D2 --> Vit D3 --> ↑ Ca++ absorption from the GIT
· PARATHYROID DISEASES: Hyperparathyroidism; Hypoparathyroidism; Pseudohypoparathyroidism
o Hyperparathyroidism:
Ø Types:
o Primary hyperparathyroidism: from a dysfunction in the parathyroid glands themselves, with oversecretion of PTH. The most common cause is a benign parathyroid adenoma (90%) that loses its sensitivity to circulating calcium levels. Usually, only one of the four parathyroid glands is affected. A less common cause is from multiple endocrine neoplasia (MEN).
o Secondary hyperparathyroidism: due to resistance to the actions of PTH, usually due to chronic renal failure. The bone disease in secondary parathyroidism along with renal failure is termed renal osteodystrophy.
Tertiary hyperparathyroidism: seen in patients with long-term secondary hyperparathyroidism, which eventually leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels. This disorder is most often seen in patients with chronic renal failure and is an autonomous activity.
o PTHrP: from SqCC of the lung, RCC, Breast cancer, multiple myeloma
Ø Evaluation: 75% asymptomatics. Moans (altered mental status, fatigue), Groans (abdominal pain, GERD, N/V, constipation), Stones (kidney), Bone (bone pain), and "psychiatric Overtones" (lethargy, fatigue, depression, memory problems). Other symptoms: HA, decreased sex drive, thinning hair, HTN, and heart palpitations which are often due to bouts of atrial fibrillation. CMP (hyperCa++, hypercalciuria, hypophosphatemia), ↑ PTH, Brown tumors.
v Brown tumor: tumors of bone arising in settings of excess osteoclast activity, such as hyperparathyroidism, and consist of fibrous tissue, woven bone and supporting vasculature, but no matrix. They are radiolucent on x-ray. The osteoclasts consume the trabecular bone that osteoblasts lay down and this front of reparative bone deposition followed by addition resorption can expand beyond the usual contour of the bone, involving the periosteum and causing bone pain. The characteristic brown coloration results from hemorrhage into the ostelytic cysts.
Ø Treatment: Acute: IVF & loop diuretics. Chronic: pre-op bisphosphonate follow by parathyroidectomy; treat underlying causes of PTHrP
Brown tumours of the hands in a patient with hyperparathyroidism.
By Frank Gaillard - Credit: Dr Ahmed Haroun submitted to Radiopaedia.org via RadPod.org, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6884362
Micrograph of a brown tumor (left of image).
By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19542202
Pepper & Salt, classical X-Ray appearance of hyperparathyroidisim
By haitham alfalah - haitham alfalah, Copyrighted free use, https://commons.wikimedia.org/w/index.php?curid=7131880
o Hypoparathyroidism: ↓ function of the parathyroid glands --> ↓ PTH --> hypocalcemia & hyperphosphatemia
Ø Evaluation: Tremor, tetany and, eventually, convulsions. Chvostek’s sign (tap CN VII --> facial spasm). Trousseau’s sign (occlude brachial artery with BP cuff --> carpal spasm). Measure serum Ca++, albumin (for correction) and PTH. If necessary, measuring urinary cAMP after an IV dose of PTH can help in the distinction between hypoparathyroidism and other causes.
Ø Treatment: IV Ca++ (e.g. calcium gluconate). Generally, a central venous catheter is recommended, as the calcium can irritate peripheral veins and cause phlebitis. Long-term treatment: Ca++ & Vitamin D3 supplementation. Teriparatide, a synthetic PTH might become the treatment of choice.
o Pseudohypoparathyroidism: kidney resistance to the PTH. Patients have a low serum Ca++ and high PO4-, but the parathyroid hormone level is appropriately high.
§ Type 1a pseudohypoparathyroidism has a characteristic phenotypic appearance (Albright's hereditary osteodystrophy), including short fourth and fifth metacarpals and a rounded facies. Gene defect from mother (GNAS1).
Type 1b pseudohypoparathyroidism lacks the physical appearance of type 1a, but is biochemically similar. Gene defect from mother (GNAS1 and STX16).
PITUITARY GLAND:
· EMBRYOLOGY: Pituitary develops from 2 different regions:
Adenohypophysis (anterior pituitary): develops from an evagination of ectoderm from the roof of the mouth (Rathke’s pouch)
Neurohypophysis (posterior pituitary): develops from an evagination of neuroectoderm from the diencephalon.
Anomalies: At times small portions of the Rathke’s pouch may continue to persist in the roof of the pharynx --> may form a pharyngeal hypophysis. Sometimes they can differentiate into craniopharyngiomas.
Located at the base of the brain, the pituitary gland is protected by a bony structure called the sella turcica of the sphenoid bone.
By Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 1180, Public Domain, https://commons.wikimedia.org/w/index.php?curid=567162
· ANATOMY: The pituitary gland sits in the sella turcica covered by a dural fold (sellar diaphragm). The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in the middle cranial fossa at the base of the brain. The optic chiasm lies anterior, the hypothalamus above, and CN III, IV, V, VI, and the ICA (internal carotid artery) lie in proximity. The pituitary gland, ICA, and CN III, IV, V1, V2, & VI all lie within the cavernous sinus. Thus the aforementioned structures are at risk for compression or invasion from a pituitary tumor. Bitemporal hemianopsia results when a pituitary tumor encroaches on the optic chiasm.
o Divisions of the Pituitary:
Ø Anterior pituitary (Adenohypophysis): functionally linked to the hypothalamus via the hypophysial-portal vascular connection in the infundibulum (or pituitary stalk). Through this vascular connection the hypothalamus integrates stimulatory and inhibitory central and peripheral signals to the five phenotypically distinct pituitary cell types.
Ø Posterior pituitary (neurohypophysis): connected to the hypothalamus via the infundibulum, giving rise to the tuberoinfundibular pathway. Hormones are made in nerve cell bodies positioned in the hypothalamus, and these hormones are then transported down the nerve cell's axons to the posterior pituitary.
Ø Intermediate lobe: In adult humans it is just a thin layer of cells between the anterior and posterior pituitary, nearly indistinguishable from the anterior lobe. The intermediate lobe produces melanocyte-stimulating hormone (MSH), although this function is often (imprecisely) attributed to the anterior pituitary.
o Arterial supply: superior hypophyseal artery, infundibular artery, prechiasmal artery, inferior hypophyseal artery, capsular artery, artery of the inferior cavernous sinus.
Histology of pituitary gland.
By Athikhun.suw - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=42343791
Cerebrum.
By Anatomist90 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=29120652
· PHYSIOLOGY:
o Anterior pituitary hormones: FLAT PiG --> FSH & LH (control gonadal function), ACTH (control glucocorticoids secretion), TSH (regulates thyroid function), PRL (necessary for lactation), GH (regulation of growth & metabolism).
Ø F _______________, _______________, _______________, _______________, _______________
Ø L _______________, _______________, _______________, _______________, _______________
Ø A _______________, _______________, _______________, _______________, ________________
Ø T _______________, _______________, _______________, _______________, _______________
Ø P _______________, _______________, _______________, _______________, _______________
Ø G _______________, _______________, _______________, _______________, _______________
o Posterior pituitary hormones: POSA --> Paraventricular nuclei --> Oxytocin (necessary for milk secretion in lactation), Supraoptic nuclei --> ADH (regulates H20 excretion)
Ø P _______________, _______________, _______________, _______________, _______________
Ø O _______________, _______________, _______________, _______________, _______________
Ø S _______________, _______________, _______________, _______________, ________________
Ø A _______________, _______________, _______________, _______________, _______________
· PITUITARY DISEASES:
o Classification: Oversecretion versus Undersecretion of hormones
Ø Oversecretion: Occur with pituitary adenoma (SEE TABLE BELOW)
Ø Undersecretion: Panhypopituitarism (↓ all anterior hormones). Diabetes insipidus (↓ ADH)
o Evaluation: Most pituitary adenoma are non-functioning.
· Non-functioning adenoma usually cause local symptoms such as HA & visual defect.
· Large adenoma compresses the optic chiasm --> bitemporal hemianopsia.
· Lack of lactation following pregnancy --> suspect Sheehan’s syndrome
· MRI with gadolinium enhancement is the gold standard for pituitary abnormality. Microadenoma: < 10mm. Macroadenoma > 10 mm. Inferior petrosal sinus sampling.
THYROID GLAND:
· EMBRYOLOGY:
o The thyroid is endodermal-derived and starts developing in the pharynx in the fetus and descends to its final position taking a path through the tongue, hyoid bone and neck muscles. The connection between its original position and its final position is the thyroglossal duct. This duct normally atrophies and closes off before birth but can remain open in some people.
o Foramen cecum: the former site of the thyroglossal duct
o Persistent thyroglossal duct: failure of the thyroglossal duct to atrophy
o Lingual thyroid: complete failure of the thyroid diverticulum to migrate from the base of the tongue.
Human thyroid
By CFCF - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=33190618
· ANATOMY: The thyroid is situated on the front side of the neck, starting at the oblique line on the thyroid cartilage (just below the laryngeal prominence or Adam's apple), and extending to the 6th Tracheal ring. In 75% of the population, the distal thyroglossal remnant extends superiorly from the isthmus and is called the pyramidal lobe.
o Arterial supply:
Ø Superior thyroid artery arises from the external carotid artery
o Inferior thyroid artery arises from the thyrocervical trunk
o Venous drainage:
Ø Superior and middle thyroid veins drain into the interal jugular vein
Ø Inferior thyroid vein drains into the brachiocephalic vein
o Key importance: The recurrent laryngeal nerve (a branch of the vagus nerve)
Ø Right recurrent laryngeal nerve loops under the right subclavian artery from anterior to posterior and ascends superiorly in the right tracheesophageal groove
Ø Left recurrent laryngeal nerve loops in a similar fashion around the arch of the aorta and ascends along the left tracheoesophageal groove
Ø Both nerves travel posteromedial to their respective thyroid lobes and enter the larynx via the cricothyroid membrane to innvervate the abductor muscles of the true vocal cords.
Ø Injury during thyroidectomy --> hoarseness secondary to ipsilateral vocal cord paralysis.
Section of a thyroid gland under the microscope. 1 follicles, 2 follicular cells, 3 endothelial cells
By Uwe Gille - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=555301
· PHYSIOLOGY: The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3), and calcitonin.
o Cells contained within the thyroid
Ø Follicular cell (aka thyroid epithelial cell): synthesize T4 & T3 from Tyrosine + Iodine.
Ø Parafollicular cell (aka C cells): synthesize Calcitonin
o Hormone function:
Ø T4 & T3 (80% of the T4 is converted to T3 by peripheral organs [via the enzyme deiodinase] such as the liver, kidney and spleen. T3 is 10X more active than T4): 4 B’s --> Brain maturation, Bone growth (matrix ossification & growth plate fusion), beta-adrenergic effects, BMR ↑ (basal metabolic rate via ↑ Na+/K+ ATPase activity)
v B _______________, _______________, _______________, _______________, _______________
v B _______________, _______________, _______________, _______________, _______________
v B _______________, _______________, _______________, _______________, ________________
v B _______________, _______________, _______________, _______________, _______________
In the blood, T4 and T3 are bound to TBG (thyroxine-binding globulin), transthyretin and albumin. Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. Only the free fraction has hormonal activity.
§ Causes of elevated TBG: PLOT --> Pregnancy, Liver disease (acute), OCP, Tamoxifen.
o P _______________, _______________, _______________, _______________, _______________
o L _______________, _______________, _______________, _______________, _______________
o O _______________, _______________, _______________, _______________, ________________
o T _______________, _______________, _______________, _______________, _______________
§ Causes of reduced TBG: LANG --> Liver disease (chronic), Androgens, Nephrotic syndrome, Glucocorticoids
o L _______________, _______________, _______________, _______________, _______________
o A _______________, _______________, _______________, _______________, _______________
o N _______________, _______________, _______________, _______________, ________________
o G _______________, _______________, _______________, _______________, _______________
Ø Calcitonin: deposit Calcium in bone.
THYROID DISEASES: HYPERTHYROIDISM; GRAVE’S DISEASE; HYPOTHYROIDISM (MYXEDEMA, CRETINISM);
Ø THYROID DISEASES: THYROIDITIS (Major types: Hard Dick Requires Puss’ --> HDRP --> Hashimoto’s, De Quervain’s, Reidel’s, and Postpartum thyroiditis); THYROID NODULES; THYROID TUMORS (Benign: THYROID ADENOMA, Malignant: Papa Feverishly Hump Mama’s Asrse = PFHMA --> Papillary cancer, Follicular cancer, Hurthle cell variant, Medullary cancer, Anaplastic cancer.
HYPERTHYROIDISM: excess of circulating free T4 or free T3, or both. Etiologies: Grave’s disease (70-80% of all cases), toxic thyroid adenoma, toxic multinodular goiter (Plummer’s disease), AIDS, pituitary TSH hypersecretion, exogenous iodide (Jod-Basedow phenomenon), struma ovarii (benign monodermal ovarian teratoma of entirely thyroid tissue)
Ø Evaluation: HEAT --> Heat intolerance, Hyperactivity, HTN, HOCF (high output cardiac failure), Extremely irritable/restless, Exophthamus, Arrhythmia, Atrial fibrillation, Anxiety, Tremor, Tachycardia, Tachypnea, Thin (weight loss)
v H _______________, _______________, _______________, _______________, _______________
v E _______________, _______________, _______________, _______________, _______________
v A _______________, _______________, _______________, _______________, ________________
v T _______________, _______________, _______________, _______________, _______________
TSH ↓, total & free T4 ↑, Thyroid antibodies (TSI-thyroid stimulating immunoglobulin, TGI-thyroid growth immunoglobulin; seen in Grave’s disease), RAIU (radioactive iodine uptake) scan, US thyroid nodules (differentiate hot versus cold nodule), Biopsy of thyroid nodules (to rule out cancer), MRI head (rule out pituitary tumor).
Thyroid storm: Severe thyrotoxicosis with N/V, fever, HOCF, tachycardia, diaphoresis. Usually occur in an individual with unknown or inadequately treated hyperthyroidism.
Ø Treatment: Anti-thyroid medications: PTU (propylthiouracil) & MTZ (methimazole) --> treatment usually last 1 year, followed by a gradual taper. If Pregnant --> use PTU because MTZ is assocated with aplasia cutis. PTU also have added benefit of reducing Peripheral conversion of T4 to T3. 131I thyroid ablation: For recurrent disease on medication. Treat with PTU before begin 131I to prevent excess release of thyroid hormone. Propanolol: for symptomatic relief of anxiety, tachycardia, and restlessness. Thyroidectomy: risk of postsurgical hypothyroidism and damage to recurrent laryngeal nerve & parathyroid glands.
GRAVE’S DISEASE (aka Grave-Basedow disease; F>M): Associated with HLA-DR3/B8
Ø Evaluation: DEPT (Graveyard department) --> Grave’s disease is aka Diffuse toxic goiter, it is associated with DR3-HLA; Exophthalmos (thyroid gland and the extraocular muscles share a common antigen --> antibodies binding to the EOM causes swelling behind the eyeball), Pretibial myxedema (non-pitting edema with thickening of the skin, described as "peau d'orange" usually found on the lower extremities), TSI (thyroid stimulating Ig) & TGI (thyroid growth Ig) are the auto-antibodies that bind to the TSH receptor and chronically stimulate it causing excessive T3 & T4 production, which leads to Thyrotixicosis. Patient also present with HEAT (see mnemomic above).
v D _______________, _______________, _______________, _______________, _______________
v E _______________, _______________, _______________, _______________, _______________
v P _______________, _______________, _______________, _______________, ________________
v T _______________, _______________, _______________, _______________, _______________
Ø Treatment: As per treatment for hyperthyroidism stated above. For eye disease:
v For mild disease - artificial tears, steroid eyedrops, oral steroids (to reduce chemosis).
v For moderate disease - lateral tarsorrhaphy (surgical procedure in which the eyelids are partially sewn together to narrow the opening)
v For severe disease - orbital decompression or retro-orbital radiation
Graves' disease symptoms
By Madhero88 at English Wikipedia, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=6553240
The classic finding of exophthalmos and lid retraction in Graves' disease
By Jonathan Trobe, M.D. - University of Michigan Kellogg Eye Center - The Eyes Have It, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=16115992
Graves’ disease. Hyperplastic follicular cells and the colloid has a "scalloped’ appearance.
CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=512564
HYPOTHYROIDISM: insufficient production of thyroid hormone by the thyroid gland. Adult: Myxedema, Child-Cretinism
Ø MYXEDEMA: A skin and tissue disorder usually due to severe prolonged hypothyroidism. It results from the accumulation of increased amounts of hyaluronic acid and chondroitin sulfate in the dermis in both lesional and normal skin. The mechanism that causes myxedema is still not yet understood, although studies suggest that thyroid hormones affect the synthesis and catabolism of mucopolysaccharides and collagen by dermal fibroblasts. It is characterized by a jelly-like infiltrations in subcutaneous tissues
Ø CRETINISM: Congenital hypothyroidism. At birth, child with P’s --> Pot-bellied, Pale, Puffy face, Protruding umbilicus, Protuberant tongue. Causes: endemic iodide deficiency, inherited mutation of genes that code for specific enzyme required for thyroid hormonogenesis, transplacental transfer of anti-thyroid Ab (eg, mother with Hashimoto thyroiditis). Delay recognition and treatment of congenital hypothyroidism beyond 3 month of age result in irreversible mental retardation.
v P _______________, _______________, _______________, _______________, _______________
v P _______________, _______________, _______________, _______________, _______________
v P _______________, _______________, _______________, _______________, ________________
v P _______________, _______________, _______________, _______________, _______________
v P _______________, _______________, _______________, _______________, _______________
Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and pallor
By Herbert L. Fred, MD and Hendrik A. van Dijk - http://cnx.org/content/m15004/latest/, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=30826141
Child affected by cretinism, associated with a lack of iodine.
By Internet Archive Book Images - https://www.flickr.com/photos/internetarchivebookimages/14780980651/Source book page: https://archive.org/stream/thyroidglandinhe00mcca/thyroidglandinhe00mcca#page/n158/mode/1up, No restrictions, https://commons.wikimedia.org/w/index.php?curid=43332690
Ø Etiologies of adult hypothyroidism: Hashimoto thyroiditis (#1 cause), iodine deficiency, iatrogenic (eg, radioactive thyroid ablation), pituitary dysfunction (↓ both TSH & T4/T3), Wolff-Chaikoff effect (hypothyroidism caused by ingestion of a large amount of iodine drugs). Drug causes of hypothyroidism: LI+ --> Li+, Iodine, IFN
v L _______________, _______________, _______________, _______________, _______________
v I _______________, _______________, _______________, _______________, _______________
Ø Evaluation: COLD --> Cold intolerance, Constipation, Carpal tunnel syndrome, Cholesterol ↑, Obese, Lower-pitched voice, Dry hair/skin, Deaf, Delay DTR (deep tendon reflex), Diastolic BP ↑, Depression, Dementia
v C _______________, _______________, _______________, _______________, _______________
v O _______________, _______________, _______________, _______________, _______________
v L _______________, _______________, _______________, _______________, ________________
v D _______________, _______________, _______________, _______________, _______________
TSH ↑, total & free T4 ↓, Thyroid antibodies (anti-thyroglobulin, anti-thyroid peroxidase, anti-TSH receptor, anti-Iodine receptor; seen in Hashimoto’s thyroiditis), RAIU scan, FLP, CPK, liver function test, CBC (anemia), CMP (euvolemic hypoNa+), CXR (pericardial effusion), MRI to evaluate pituitary tumor.
Myxedema coma: ultimate stage of long-standing untreated hypothyroidism. Symptoms: slowly progressive dementia, delirium, and in extreme cases to hallucinations, coma, or psychosis, particularly in the elderly. Associated with very high rate of mortality.
Ø Treatment: L-thyroxine (start low & ↑ dose to therapeutic level over 4-6 months). Myxedema coma: IV L-thyroxine, steroids, warming blanket, ventilatory support.
THYROIDITIS
Ø Major types: Hard Dick Requires Puss’ --> HDRP --> Hashimoto’s, De Quervain’s, Reidel’s, and Postpartum thyroiditis.
v H _______________, _______________, _______________, _______________, _______________
v D _______________, _______________, _______________, _______________, _______________
v R _______________, _______________, _______________, _______________, ________________
v P _______________, _______________, _______________, _______________, _______________
Ø H ASHIMOTO’s thyroiditis (#1, aka struma lymphomatosa): An autoimmune disease where the body's own antibodies attack the cells of the thyroid. F > M 20:1. Most prevalent between 45 and 65 years of age.
v Evaluation: Hashimoto's thyroiditis usually results in hypothyroidism, although in its acute phase, it can cause a transient thyrotoxic state. Painless thyroid enlargement. HASHI --> associated with HLA-DR5 & B5 and Hurthle cell changes (a large cell often associated with follicular thyroid cancer & usually stains pink); it is an Autoimmune disease with Anti-thyroglobulin, Anti-thyroid peroxidase, Anti-TSH receptor, Anti-Iodine receptor (these auto-Ab cause gradual destruction of follicles in the thyroid gland), the disease follows a Slow course leading to eventual Hypothyroidism; histology: Infiltration of T-lymphocytes into thyroid stroma with formation of germinal centers; it is associated with an Increase of other autoimmune diseases (DM, Pernicious anemia, Sjogren’s syndrome).
§ H _______________, _______________, _______________, _______________, _______________
§ A _______________, _______________, _______________, _______________, _______________
§ S _______________, _______________, _______________, _______________, ________________
§ H _______________, _______________, _______________, _______________, _______________
§ I _______________, _______________, _______________, _______________, _______________
v Treatment: L-thyroxine.
A thyroid gland with Hashimoto's thyroiditis showing lymphocytic inflammation with germinal center formation
By Librepath - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=45578566
Ø D E QUERVAIN’s thyroiditis (aka subacute granulomatous thyroiditis or subacute thyroiditis): Usually occurs in women between 30-50 y/o.
v Evaluation: Some cases may be viral in origin (mumps, coxsackie virus) --> URI symptoms, malaise, fever, extremely TENDER thyroid. Patients will experience a hyperthyroid period as the cellular lining of colloid spaces fails, allowing abundant colloid into the circulation. Patients typically then become hypothyroid as the pituitary reduces TSH production and the inappropriately released colloid is depleted before resolving to euthyroid. 123I uptake ↓. T3 & T4 ↑ in initial phase.
v Treatment: NSAID. Corticosteroids may be of help in refractory cases
A granuloma in subacute thyroiditis.
By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18491382
Ø R IEDEL’S thyroiditis (aka Riedel’s struma): A chronic fibrosing form of thyroiditis and may be a presentation of IgG4 disease.
v Evaluation: Characterized by the replacement of the normal thyroid parenchyma by a dense fibrosis tissue. Thyroid adheres to neighboring structure --> immobile thyroid on physical exam, which mimic thyroid carcinoma.
Ø P OSTPARTUM thyroiditis: a transient phenomenon observed following pregnancy and may involve hyperthyroidism, hypothyroidism or the two sequentially. It is believed to result from the modifications to the immune system necessary in pregnancy, and histologically is a lymphocytic thyroiditis. The process is normally self-limiting, but when conventional antibodies are found there is a high chance of this proceeding to permanent hypothyroidism.
Treatment: Hyperthyroidism may be treated with a beta-blocker, while hypothyroidism requires replacement with levothyroxine
THYROID NODULES: Common and ↑ with age. Most are benign.
Ø Evaluation: Single discrete nodule in a single lobe to large bulky disease with distant metastasis. The nodule has ↑ risk of being a malignancy if: history of neck irradiation (especially papillary thyroid cancer), cold nodule, appeared firm & fixed to surround structure, and NON-TENDER. Hoarseness (due to recurrent laryngeal nerve compression), dysphagia (from esophagus compression) may also be present. TFT. TSH. US (suspicious findings in a nodule are solid state, hypoechoic, irregular borders, microcalcifications, high internal vascularity). 123I scan (demonstration functional status of a nodule into cold versus hot; hot ones takes up high levels of radioactive iodide tracer). FNA biopsy (the most important test).
Ø Treatment: Benign: treat with L-thyroxine to feedback inhibit TSH release --> shrink tumor. Malignant: Surgical resection. Unclear status: lobectomy.
THYROID TUMORS
Ø Benign:
v THYROID ADENOMA: distinguished from a multinodular goiter of the thyroid in that an adenoma is typically solitary, and is a neoplasm resulting from a genetic mutation (or other genetic abnormality) in a single precursor cell. In contrast, a multinodular goiter is usually thought to result from a hyperplastic response of the entire thyroid gland to a stimulus, such as iodine deficiency. A thyroid adenoma may be clinically silent, or it may be a "functional" tumor, producing excessive thyroid hormone resulting in symptomatic hyperthyroidism, and may be referred to as a toxic thyroid adenoma. Careful pathological examination may be necessary to distinguish a thyroid adenoma from a minimally invasive follicular thyroid carcinoma.
A thyroid nodule
By myself - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=6297727
Ø Malignant: Papa Feverishly Hump Mama’s Ass = PFHMA --> Papillary cancer, Follicular cancer, Hurthle cell variant, Medullary cancer, Anaplastic cancer.
v P _______________, _______________, _______________, _______________, _______________
v F _______________, _______________, _______________, _______________, _______________
v H _______________, _______________, _______________, _______________, _______________
v M _______________, _______________, _______________, _______________, ________________
v A _______________, _______________, _______________, _______________, _______________
Ø P APILLARY CARCINOMA: This is the most common type of thyroid cance (80%). F > M. Presents in the 30-40 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck (in this group, the cancer tends to be multifocal with early lymphatic spread, and portends a relatively poor prognosis). Thyroglobulin can be used as a tumor marker for well-differentiated papillary thyroid cancer.
v Evaluation: Characteristic Orphan Annie eye nuclear inclusions and psammoma bodies on Light Microscopy. Lymphatic spread is more common than hematogenous spread. Multifocality is common. Molecular: Chromosomal translocations involving the RET proto-oncogene (encoding a tyrosine kinase) located on chromosome 10q11 occur in approximately a fifth of papillary thyroid cancers, translocations involving the gene NTRK1 (encoding the TrkA receptor), located on chromosome 1q in approximately 5-10% of papillary thyroid cancers, and point mutations in the BRAF oncogene (V600E) is seen in a third to a half of cases. These mutations activate the MAPK/ERK pathway.
v Treatment: < 1 cm & confined to 1 lobe: lobectomy. > 1 cm: total thyroidectomy, and central compartment lymph node removal is the therapy of choice. However, due to the multifocality & bilaterallity nature of papillary cancer, total thyroidectomy may leads to better long-term survival in all cases.
Cytology of Papillary Carcinoma of the Thyroid: Cellular crowding and overlapping, nuclear grooves, and pseudoinclusion.
By Ed Uthman, MD - http://www.flickr.com/photos/euthman/481523439/, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=2047540
Histology of Papillary Carcinoma of the Thyroid: groove formation, optical clearing, eosinophilic inclusions and overlapping of nuclei.
By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=502860
Ø F OLLICULAR CARCINOMA: more commonly in F > 50 y/o. More common in iodine deficient area.
v Evaluation: Usually present as a solitary mass. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. It is not possible to distinguish between follicular adenoma and carcinoma on cytological grounds. If FNA cytology suggests follicular adenoma, thyroid lobectomy should be performed to establish the histopathological diagnosis. Follicular carcinoma tends to metastasize to lung and bone via the bloodstream, while papillary thyroid carcinoma commonly metastasizes to cervical lymph nodes. Molecular: mutations in the Ras subfamily of oncogenes, most notably HRAS, NRAS, and KRAS, occur in about one-half of cases, while chromosomal translocation between paired box gene 8 (PAX-8) and the gene encoding peroxisome proliferator-activated receptor γ 1 (PPARγ1), leading to the fusion protein PAX8-PPARγ1 is present in approximately one-third of follicular thyroid carcinomas, specifically those cancers with a t(2;3)(q13;p25) translocation.
v Treatment: Unilateral hemithyroidectomy is uncommon. Total thyroidectomy is almost automatic due to the aggressive nature of this form of thyroid cancer. This is invariably followed by radioiodine treatment at levels from 50 to 200 millicuries following two weeks of a low iodine diet (to optimize the takeup of the radioactive iodine dose.). 131I is used for ablation of the thyroid tissue.
Ø M EDULLARY CARCINOMA: Originates from the parafollicular cells (C cells), which produce the hormone calcitonin. While the increased calcitonin itself is probably not harmful, it is useful as a marker which can be tested in blood. A second marker, carcinoembryonic antigen (CEA), is also produced by medullary thyroid carcinoma. Its prognosis is poorer than that of follicular and papillary thyroid cancer when it has metastasized beyond the thyroid gland. 25% of the cancer develops in families, both in isolated form (termed familial medullary thyroid carcinoma) or as part of the syndrome of multiple endocrine neoplasia MEN type 2 and 2B. Hereditary medullary thyroid cancer is inherited as an autosomal dominant trait. 75% of medullary thyroid carcinoma occurs in individuals without an identifiable family history and is assigned the term "sporadic". Individuals who develop sporadic medullary thyroid carcinoma tend to be older and have more extensive disease at the time of initial presentation than those with a family history. It is associated with mutations in the RET proto-oncogene on chromosome 10, lead to the expression of a mutated receptor tyrosine kinase protein, termed RET. RET is involved in the regulation of cell growth and development and its mutation is responsible for nearly all cases of hereditary or familial medullary thyroid carcinoma.
v Evaluation: The major clinical symptom of medullary thyroid carcinoma is diarrhea; occasionally a patient will have "flushing" episodes, particularly with liver metastasis. Sites of spread of medullary thyroid carcinoma include local cervical & mediastinal lymph nodes, liver, lung, and bone. Biopsy: sheets of tumor cells lying in a stromal AMYLOID deposit.
v Treatment: Total thyroidectomy. Unlike differentiated thyroid carcinoma, there is no role for radioiodine treatment in medullary-type disease. External beam radiotherapy should be considered for patients at high risk of regional recurrence, even after optimum surgical treatment.
Medullary thyroid carcinoma on ultrasound with typical small calcifications (arrows)
By Hellerhoff - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8337552
Medullary thyroid carcinoma (MTC). Medullary thyroid carcinoma with amyloid deposition (left). Normal thyroid follicles are also seen (right of image).
. MTC can be remembered by the 3 Ms: aMyloid. Median node dissection. MEN 2A & MEN 2B. It typically stains with: Calcitonin. CEA. Chromogranin A. Multiple endocrine neoplasia 2A: Medullary thyroid carcinoma. Parathyroid adenoma. Pheochromocytoma. Multiple endocrine neoplasia 2B: Medullary thyroid carcinoma. Pheochromocytoma. Neuromas/ganglioneuromas.
By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17252610
Ø H URTHLE CELL CARCINOMA: A variant of follicular cell carcinoma. Hurthle cell forms are more likely than follicular carcinomas to be bilateral and multifocal and to metastasize to lymph nodes. Like follicular carcinoma, unilateral hemithyroidectomy is performed for non-invasive disease, and total thyroidectomy for invasive disease
Ø A NAPLASTIC CARCINOMA: Has a very poor prognosis (near 100% mortality) due to its aggressive behavior and resistance to cancer treatments.
v Evaluation: It rapidly invades surrounding tissues (such as the trachea). The presence of regional lymphadenopathy in older patients in whom FNA reveals characteristic vesicular appearance of the nuclei would support a diagnosis of anaplastic carcinoma.
v Treatment: Unlike its differentiated counterparts, anaplastic thyroid cancer is highly unlikely to be curable either by surgery or by any other treatment modality, and is in fact usually unresectable due to its high propensity for invading surrounding tissues. Palliative treatment consists of radiation therapy usually combined with chemotherapy. New drugs, such as Bortezomib and TNF-Related Apoptosis Induced Ligand (TRAIL) are being trialed in clinical labs.
Anaplastic thyroid cancer in Ultrasound
By Mme Mim - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=37073531
Anaplastic thyroid carcinoma with a component of papillary thyroid carcinoma tall cell variant
By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8298744
ENDOCRINOLOGIC SYNDROMES:
Ø MULTIPLE ENDOCRINE NEOPLASIA: Inherited as autosomal dominant disorders. Types:
v MEN TYPE I (Wermer's syndrome): Caused by MEN1 gene at 11q13 which encodes a nuclear protein called menin that is believed to act as a tumor suppressor.
§ Evaluation: 3 P’s --> Pituitary adenoma (may cause pituitary hormone excess). Pancreatic islet cell tumours causing hypoglycaemia (insulinoma) and Zollinger-Ellison syndrome (gastrinoma), Parathyroid hyperplasia/tumour causing hyperparathyroidism.
o P _______________, _______________, _______________, _______________, _______________
o P _______________, _______________, _______________, _______________, _______________
o P _______________, _______________, _______________, _______________, _______________
Pituitary adenoma
By Yakafaucon - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2990860
CT image showing a mass in the pancreas
By MBq at German Wikipedia - Transferred from de.wikipedia to Commons.(Original text: selbst erstellt), Public Domain, https://commons.wikimedia.org/w/index.php?curid=2163329
Parathyroid adenoma
By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27924389
v MEN TYPE II (Sipple’s syndrome): The mutation is in the RET proto-oncogene on chromosome 10.
§ Evaluation: ATP --> Adrenal pheochromocytoma, Thyroid medullary carcinoma associated with increased calcitonin secretion (test for elevation of calcitonin after pentagastrin injection and/or calcium infusion), Parathyroid hyperplasia or tumour causing hyperparathyroidism.
o A _______________, _______________, _______________, _______________, _______________
o T _______________, _______________, _______________, _______________, _______________
o P _______________, _______________, _______________, _______________, _______________
Pheochromocytoma. CT abdomen.
By Unknown - http://www.cc.nih.gov/ccc/papers/vonhip/adrenal.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=5622670
Medullary thyroid carcinoma on ultrasound with typical small calcifications (arrows)
By Hellerhoff - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8337552
Parathyroid adenoma
By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=27924389
v MEN TYPE IIb or III:
§ Evaluation: ATM --> Adrenal pheochromocytoma. Thyroid medullary carcinoma. Mucosal neuromas which are usually situated in the gastrointestinal tract. Marfanoid habitus (50%).
o A _______________, _______________, _______________, _______________, _______________
o T _______________, _______________, _______________, _______________, _______________
o M _______________, _______________, _______________, _______________, _______________
Pheochromocytoma. CT abdomen.
By Unknown - http://www.cc.nih.gov/ccc/papers/vonhip/adrenal.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=5622670
Medullary thyroid carcinoma on ultrasound with typical small calcifications (arrows)
By Hellerhoff - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8337552
A positive wrist sign in a patient with Marfan syndrome. In case of a positive wrist sign the thumb and little finger overlap, when grasping the wrist of the opposite hand.
By Staufenbiel I, Hauschild C, Kahl-Nieke B, Vahle-Hinz E, von Kodolitsch Y, Berner M, Bauss O, Geurtsen W, Rahman A - http://www.ncbi.nlm.nih.gov/pubmed/24165013, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=42107027
Disneyworld, Orlando, Florida, USA!