Endocrinology Flashcards
Carcinoid syndrome
Diarrhea, Flushing, Wheezing
– Carcinoid Heart Disease (Right sided endcardial fibrosis and thickening of heart valves secondary to exposure to serotonin)
– Vitamin B3 deficiency (Pellagra > Diarhea, Dermatitis, Dementia), Vit-B3 def is because Tryptophan which is also a precursor for Vit-B3 gets shunted more towards production of serotonin therefore Vit-B3 level decrease.
– Elevated 24-hr urinary excretion of 5-HIAA.
– Octreotide for symptomatic patients.
Von Hippel-Lindau syndrome
VHL gene mutation (chromosome 3).
- Hemangioblastomas
- Clear cell renal carcinoma
- Pheochromocytoma
5-Alpha Reductase Def
- 46,XY genotype
- Impaired conversion of testosterone to DHT
- Male internal genitalia (eg, testes, vas deferens)
- Female external genitalia (eg, blind-ending vagina)
- Phenotypically female at birth
- Normal male testosterone & estrogen levels
- DHT promotes development of male external genetalia and prostate from genital tubercle and urogenital sinus
21 Hydroxylase Deficiency
- Increased 17-hydroxyprogesterone
- Increased testosterone
- hypotension, hyponatremia, and hyperkalemia
- Low Cortisol and Aldosterone
- Low BP
17-Alpha hydroxylase deficiency
- XY: atypical genitalia, undescended testes
- XX: lacks 2° sexual development
- The only one that presents with genital virilization in Males
- Hypokalemia, Hypernatremia, Hyperglycemia
Neurofibromatosis type I
- Café-au-lait spots,
- Lisch nodules (iris hamartoma),
- cutaneous neurofibromas,
- pheochromocytomas,
- optic gliomas
Neurofibromatosis type II
Bilateral vestibular schwannomas
Acute adrenal insufficiency (adrenal crisis)
- Body make too little Aldosterone & Cortisol
- Shock, altered mental status, vomiting, abdominal pain, weakness, fatigue in patient under glucocorticoid therapy.
Addison disease
- Chronic 1° adrenal insufficiency
- Increase ACTH, Increase MSH
- Decrease Aldosterone & Cortisol
- Skin hyperpigmentation, orthostatic hypotension, fatigue, weakness, muscle aches, weight loss, GI disturbances.
Sheehan syndrome
- (severe postpartum hemorrhage leading to pituitary infarction)
- No lactation postpartum, absent menstruation, cold intolerance
- Postpartum hemorrhage in pituitary, no LH or FSH = no periods, hyperplasia infarcts; no prolactin = no milk
McCune-Albright syndrome
- (Gs-protein activating mutation)
- Skin Problem + Bone deformity + Endocrine problems
- Café-au-lait spots (unilateral),
- Polyostotic fibrous dysplasia
- Multiple endocrine abnormalities
- Precocious Puberty
Insulinoma
- Tumor of pancreatic islet cells (Beta-cell tumor)
- Hypoglycemia
- High Insulin, High C-peptide
Whipples traid:
- Hypoglycemia.
- Mental symptoms induced by fasting or exercise.
- Symptoms relieved by IV glucose.
Glucagonoma
- Rare pancreatic tumor (Alpha cell tumor)
- Increase HbA1c , Increase Insulin , Increase Glucagon.
- Wt.loss , Depression , Necrolytic Rash
- New onset of Diabetes (Hyperglycemia) with Necrolytic migratory erythema → Glucagonoma.
Vipoma
- Rare tumor assosiated with Multiple Endocrine Neoplasia (MEN)
- Also termed as WDHA syndrome
- Watery Diarrhea, Hypokalemia, Achlorhydria (absence of HCl in gastric secretions)
- Hyperglycemia (fasting state sensed by body)
- Hypercalcemia
Hyper Parathyroidism
- Presents as:
Hypercalcemia, Recurrent Nephrolithiasis, Bone pain from osseous resorption, Polyuria, Constipation, Psychiatric disturbance. - MCC parathyroid chief cell adenoma
- ↑ PTH , ↑ Ca+2 , ↓ PO4-
Zollinger-Elison Syndrome
(ZES)
Traid of:
- Pancreatic/Duodenal tumor (Gastrinoma)
- Increase Gastric secretion (Non responsive to antiacids)
- Peptic Ulcer (Distal Duodenal Ulcer)
Other symptoms:
- Diarrhea
- Abdominal pain
- Malabsorbtion
- Post-prandial pain
Gastrin increases in response to exogenus Secretin (normally Secretin inhibits gastrin production in ZES effect is opposite)
Metabolic Syndrome
- Wt.gain , Diabetes , Hyperlipidemia
- Atypical antipsychotics have highest risk of causing metabolic syndrome (i.e clozapine, olanzipine, quetiapine)
SIADH
( Syndrome of Inappropriate Anti-Diuretic Harmone )
- Too much ADH (Vasopressin)
- ADH is produced by supraoptic nucleus of hypothalamus and stored in posterior pituitary.
- ADH increases water reabsorption in medullary collecting duct.
- ↓ Serum Osmolality , ↓ Serum specific gravity
- ↓ serum Na (< 135)
- ↑ Urine osmolality , ↑ Urine specific gravity
Tx :
- Demeclocycline (tetracycline causes insenstivity to ADH).
- Conivaptan & Tolvaptan (ADH receptor antagonists).
Diabetes Insipidus ( DI )
Central DI :
- Not enough ADH secrection by hypothalamus or posterior pituitary is unable to release it properly
- Tx : Desmopressin.
- Can be caused by head trauma, meningitis or cancer.
Nephrogenic DI :
- Insensitvity to ADH in kidney (serum ADH is ↑)
- Caused by Lithium, demeclocycline, hypercalcemia, NSAIDs
- Tx : NSAIDs + Thiazide.
Labs:
- ↑ Serum Sodium (>145), ↑ Serum Osmolality,
- ↑ Serum specific gravity.
- ↓ urinary osmolality, ↓serum specific gravity.
Neuroblastoma
- Adrenal medullary tumor in kids (< 4 yrs ).
- Irregular abdominal tumor, can cross the midline.
- Urine Metanephrines HVA (homovanillic acid)
VMA (vaniylmandelic acid). - Homer-wright rosettes.
- N-myc oncogene.
- Bombesin +
- Neuron-specific enzyme +
- Opsoclonus (Dancing eyes)
- Myoclonus (Dancing feet)
Wilms Tumor
- Renal cell tumor in kids ( < 10yrs ).
- Smooth doesnot cross the midline.
- Elevated Metanephrines (HMA & VMA) in urine.
Pheochromocytoma
Adrenal Medulla tumor.
Short episodes of sympathetic hyperactivity:
- Palpitations
- Perspiration
- Pallor
- HTN (very high BP)
- Headaches
- Elevated Catecholamines (Norepi, Epi)
- Elevated Metanephrines (HMA & VMA) in urine
Tx:
- Block adrenergic receptors
1- start with alpha blockers first
2- then start beta blockers (if u give beta blockers first it can kill the patient)
Hashimotos Thyroiditis
- Hypothyroidism
- ↑TSH , ↓T3 , ↓T4 , ↓Iodine uptake.
- Leads to Thyroid gland Atrophy
- Aka Chronic Lymphocytic Thyroiditis.
Auto immune:
- Anti TPO antibodies
- Anti-Thyroglobulin antibodies
- Has Hurthle cells and germinal centers on histology, Lymphocytic infiltrates are also seen.
- Increased risk of Non-Hodgkins Lymphoma.
- Assossiated with HLA-DR 5
- Also assossiated with Thyroid Lymphoma
Congenital Hypothyroidism
Aka Cretinism.
Caused by:
1- Maternal Iodine deficiency (most common cause worldwide)
2- Congenital Thyroid abnormalities (most common cause in the developed countries)
Presents as;
- Hypotonia.
- Jaundice.
- 6 Ps
(Potbelly, Protruding Umbilicus, Protruding tounge, Puffy face, Pale, Poor brain development)
Graves disease
- Hyperthyroidism.
- ↓ TSH, ↑ T3 , ↑T4 , ↑Iodine uptake.
- Autoimmune (Stimulatory autoantibodies mimic TSH → Hyperthyroidism).
- TSH receptor antibody (TRAb) aka TSI- thyroid stimulating immunoglobulin.
- Diffuse thyroid enlargement.
- Exopthalmos/ Proptosis
(Glycosaminoglycan accumulation in and around extra occular muscles) - Peritibial myxedema
THYROID STORM:
- Fever, HTN, ↑CK.
- Sympathetic overload (Agitation, Diarrhea, Diaphoresis)
- Death (usually by arrhythmia)
- Tx : Propanolol, PTU, Prednisone
Papillary Thyroid Carcinoma
- Most common thyroid cancer
- Excellent prognosis
- Assosiated with childhood radiation
- Lymphatogenous spread
- Finger-like or Nipple like projections on histology
- Orphan-annie eye nucleus on histology
- Pasamoma bodies may also be seen on histology.
Note : Thyroid cancers are not Hyperthyroid conditions.
Medullary Thyroid Carcinoma
- Parafollicular cell tumor → ↑ Calcitonin.
- Assosiated with MEN syndrome
- Poor Prognosis- Hematogenous spread.
- Amyloid deposits in thyroid.
- Stained by Congo-Red stain.
Note : Thyroid cancers are not Hyperthyroid conditions.
Cancers with Psammoma bodies
“ PSaMM “
- P = Papillary thyroid CA.
- Sa = Serous cystadenoma/ adenocarcinoma.
- M = Meningioma.
- M = Mesothelioma.
Somatostatinoma
- Pancreatic Delta-cell tumor → secretes Somatostatin.
- Global GI inhibition.
- Steatorhea.
- Gallstones.
- Mild diabetes.
Tx: Oral hypoglycemics
MEN Syndromes
(Multiple Endocrine Neoplasia)
Autosomal dominant syndromes
→ MEN 1 : Menin gene
“ P P P “ - Pituitary adenoma. - Parathyroid adenoma. - Pancreatic adenoma.
→ MEN 2A : Marfanoid habitus
“ P M P “ - Parathyroid adenoma. - Medullary thyroid carcinoma. - Pheochromocytoma.
→ MEN 2B : Marfanoid habitus
“ P M N “ - Pheochromocytoma. - Medullary thyroid carcinoma. - Neuromas (mucosal).
Both MEN 2A and 2B have RET gene mutation
CONN syndrome
- Primary Hyper Aldosteronism
- Excess aldosterone secretion independant of RAAS.
- Renin level ↓
- Traid:
1- Hypertension
2- Hypernatremia
3- Hypokalemia - Other symptoms include:
Fatigue, Muscle cramping, chronic Headaches, Muscle weakness and pain.
Cushing Syndrome
- Increase levels of Cortisol
- (CRH → ACTH → Cortisol)
- Caused by longterm Glucocorticoid use (MCC), Pituitary tumor (Cushings disease), Ectopic ACTH secreting tumor (SCLC), Adrenal tumor.
Symptoms:
- Moon faces
- Buffalo hump
- Central Obesity & Peripheral wasting/thinning
- Abdominal Striate (stretch marks)
- Skin/ Bone thinning
- In females it causes
→ Loss of Libido.
→ Menstural changes.
→ Hirsutism.
Dx :
- ↑ 24hr urinary free costisol.
- Low/High dose Dexamethasone test.
Medullary thyroid carcinoma
- Derived from parafollicular (C) cells, which normally secrete calcitonin.
- Histopathology of a thyroid mass shows amyloid deposits amongst nests of tumor cells.
What is pituitary apoplexy?
- Acute pituitary hemorrhage.
- It usually occurs in the setting of a preexisting pituitary adenoma.
Symptoms include:
- Severe headache
- Bitemporal hemianopsia (due to compression of the optic chiasm)
- Ophthalmoplegia (due to compression of the oculomotor nerve [CNIII])
Tertiary hyperparathyroidism
- Typically occurs in the setting of long-standing chronic kidney disease/end-stage renal disease (chronic parathyroid stimulation → parathyroid hyperplasia/autonomous hormone secretion).
It is characterized by:
- (↑) serum calcium
- (↑) serum phosphate
- (↑) serum parathyroid hormone
Patient with hypocalcemia, hyperphosphatemia, elevated parathyroid hormone
These labs are consistent with (secondary) hyperparathyroidism, which is commonly caused by chronic kidney disease.
Neuroblastoma
- Young child with large abdominal mass.
- Urine shows elevated catecholamine metabolites.
- Biopsy shows small, round, blue tumor cells.
- This tumor is of neural crest cell origin.
Pseudohypoparathyroidism
- Is characterized by parathyroid hormone (resistance).
Expected labs:
- (↓) serum calcium
- (↑) serum phosphate
- (↑) serum parathyroid hormone
- Caused by defects in PTH receptor and downstream signaling (eg, Albright hereditary osteodystrophy).
Name 2 stains that indicate a tumor has neuroendocrine differentiation:
- Chromogranin
- Synaptophysin
Tumors derived from neuroendocrine cells characteristically show a salt and pepper chromatin pattern.
Waterhouse-Friderichsen syndrome is a potential complication of?
- Meningococcemia.
- It is characterized by bilateral hemorrhagic infarction of adrenal glands, resulting in acute adrenal insufficiency (eg, worsening shock).
Acute adrenal insufficiency (adrenal crisis)
- Body make too little Aldosterone & Cortisol
- Shock, altered mental status, vomiting, abdominal pain, weakness, fatigue in patient under glucocorticoid therapy.
Addison disease
- Chronic 1° adrenal insufficiency
- Inc ACTH, Inc MSH, dec Aldosterone & Cortisol
- Skin hyperpigmentation, orthostatic hypotension, fatigue, weakness, muscle aches, weight loss, GI disturbances.
Catecholamine Synthesis
- Tyrosine → DOPA (Tyrosine Hydroxylase)
- DOPA → Dopamine (Dopa Decarboxylase)
- Dopamine → Norepinephrine (Dopamine β hydroxylase)
- Norepinephrine → Epinephrine (Phenyl ethanolamine-N-methyltransferase, PNMT) + (Cortisol)
Thyrotropin (TSH) Receptor Antibody
Graves disease
Thyroid Per Oxidase (TPO) antibodies
Hashimoto’s thyroditis aka Chronic lymphocytic thyroditis
Primary hypothyroidism
- Thyroid dysgenesis
- TSH resistance
- ↓ Free & total T4 , ↑ TSH
Thyroid hormone resistance
- ↑ Free & total T4
- ↑ TSH
Central hypothyroidism
- ↓ Free & total T4
- ↓ TSH
Transient congenital hypothyroidism due to maternal exposure
- Iodine excess or deficiency
- TSH receptor–blocking antibodies
- Antithyroid medications
- ↓ Free & total T4 , ↑ TSH
