Endocrine

Tumors

Pituitary Adenoma

Prolactin level of >200 ng/mL or Repeat level of >100 ng/mL suggests the presence of prolactinoma

• If Asymptomatic & < 1cm ⇒ Periodic MRIs and serum prolactin levels

• If ≥1cm OR symptomatic (decreased Estrogen/Testosterone effects OR Increased ICP) ⇒ Dopamine Agonists
• If ttt fails (persistent symptoms/hyperprolactinemia/size/intolerance) ⇒ Transsphenoidal Surgery

• If ≥3 cm ⇒ Transsphenoidal surgery

 

Dopamine Agonists (Cabergoline & Bromocriptine) normalize prolactin levels & reduce tumor size

 

Non-functioning Pituitary Adenoma causes:

• Increased PRL (due to disruption of dopaminergic fibers)

• Decreased TSH, FSH, LH due to compression of adjacent cells

 

Hyperprolactinemia (due to drugs like antipsychotics- NOT Aripiprazole)

• Increased in PRL

• Decreased in FSH & LH

• NORMAL TSH

 

Complication is Hypopituitarism:

• Central AI → Weakness, Fatigue, Hypoglycemia, Eosinophilia, and Pale skin (low ACTH/MSH)

• Normal Aldosterone

• Hypogonadotropic Hypogonadism (Low FSH & LH) → decreased Libido, ED, testicular Atrophy

• Central Hypothyroidism → Cold Intolerance, Constipation, Bradycardia

VIPoma

• Dx → VIP levels > 75pg/mL confirms the diagnosis
• Followed by CT/MRI to localize the tumor (most common is tail of pancreas)

• Management is
• IV fluids for dehydration
• Octreotide for diarrhea
• Hepatic resection if metastasized to liver (most do)

• Presentation:
• WDHA syndrome → Watery Diarrhea, Hypokalemia, Achlorhydria
• Others → Episodic flushing + hyperglycemia + hypercalcemia (due to MEN association)

MEN Syndromes

• Pituitary Adenoma (Prolactinoma)

• Pancreatic Tumor (MC is gastrinoma)

• Parathyroid Adenoma

• Medullary Thyroid Carcinoma

• Pheochromocytoma

• Parathyroid Adenoma

• Medullary Thyroid Carcinoma

• Pheochromocytoma

• Mucosal Neuroma/Marfanoid Habitus

• This is because MTC removal surgery can predispose patient to hypertensive crisis due to asymptomatic pheochromocytoma

• If found, pheochromocytoma should be removed BEFORE MTC

Adrenal Disorders

Pheochromocytoma

• Presentations:
• Asymptomatic MEN Syndromes/NF1/VHL
• Classical Triad of episodic Headache, Sweating, and Tachycardia
• Resistant HTN or HTN with unexplained hyperglycemia

• Dx → Urine/Plasma free metanephrines followed by CT

• Management:
• Pre-operative initiation of alpha blocker BEFORE beta blocker

Cushing Syndrome

• Presentation: Female with hx of autoimmune disease + painless proximal muscle weakness + hirsutism + hypertension + osteoporosis + weight gain

• Myopathy → proximal muscle weakness with NO pain
• Associated with atrophy (impaired regeneration, not due to direct damage) → so normal ESR and CK

• Dx → ≥ 2 out of 3 should be abnormal
1. Late-Night salivary cortisol assay
2. 24-hour urine free cortisol
3. overnight low dose dexamethasone suppression test
 
• If hypercortisolism is confirmed, ACTH levels are measured.

Nonclassical CAH

• Presents as a young female with hirsutism, irregular menses, and severe acne (virilization is RARE) OR Male with peripheral precocious puberty

• Due to partial 21-a-hydroxylase deficiency (partial so no hypoaldosteronism/hypocortisolism → normal blood pressure & no salt wasting)

• Dx → HIGH 17-hydroxyprogesterone that is then converted into androgens
• Confirmed by exaggerated increase in 17-hydroxyprogesterone in response to ACTH stimulation test

Classical CAH

• 21-a-hydroxylase deficiency is a newborn presents as virilization only
• Salt-wasting, electrolyte abnormalities DON’T occur until age of 1-2 weeks due to presence of maternal adrenal hormones
• If suspected, ttt should be started: glucocorticoids & mineralocorticoids

Evaluation of Suspected Hyperaldosteronism

Primary Hyperaldosteronism (Conn Syndrome)

• Elevated plasma aldosterone & low plasma renin ⇒ Ratio > 20
• Symptoms → Hypertension, Hypokalemia, Metabolic Alkalosis, with normal/slightly increased sodium (due to Na escape), so no volume overload

• Absence of aldosterone suppression with oral saline (oral NaCl load causes suppression of renin)
• After dx, do CT scan to determine if adenoma or bilateral hyperplasia (more common)
• If bilateral adrenal hyperplasia, give Spironolactone OR Eplerenone
• If Unilateral adenoma, Surgical resection is preferred
• If patient declines surgery or can’t tolerate it, give Spironolactone OR Eplerenone

 

 

Primary Adrenal Insufficiency

• Causes → Autoimmune adrenalitis (most common), TB, Metastatic infiltration

• Features:
• NO ALDO → Hypotension, Salt wasting, orthostasis
• NO Cortisol → Weakness, Fatigue, Eosinophilia
• Increased ACTH → skin/mucus membranes hyperpigmentation
• IN WOMEN → NO ANDROGEN → loss of libido & decreased sexual hair (pubic)
• Normocytic Anemia & Abdominal pain is also present

• Dx → Cosyntropin stimulation test (synthetic ACTH) shows LOW cortisol production

 

Secondary Adrenal Insufficiency

• Causes → Sheehan Syndrome, Exogenous glucocorticoids, and Hypophysis Lymphocytic Infiltration
• Decreased ACTH, Decreased Cortisol, NORMAL Aldosterone (Normal K)

Diabetes/Glucose Disorders

Hyperosmolar Hyperglycemic State (HHS)

• Presents in an elderly patient with T2DM over days-weeks

• Risk Factors → Trauma, Infection, Acute Illness, Drugs that cause hyperglycemia (glucocorticoids, thiazides, atypical antipsychotics)

• Presentation: Severe hyperglycemia (> 1000) causing osmotic diuresis & severe dehydration [aka AMS + Dehydration + Polyuria in patient with T2DM]
• Decrease in GFR → worsening of hyperglycemia
• High plasma osmolality → Neurological symptoms (confusion → coma)
• Expected labs:
• High glucose (> 600)
• High serum osmolality (>320)
• Bicarbonate is > 18 (NO acidosis)
• pH > 7.3 (Normal anion gap)
• NO KETONES

• Management:
1. Aggressive Rehydration (Crystalloids or Normal Saline)
2. IV Insulin
3. Replace potassium if K < 5.3 (masked)

• wtf is corrected serum sodium?
• In these patients the sodium will be low, however this is not the correct concentration.
• Correct serum Sodium = measured serum sodium + 2 mEq/L for every 100mg/dl that glucose > 100 mg/dL

DKA

• Serum anion gap, electrolytes, and venous pH (every 2-4hours)

• Serum glucose (every hour)

Hypoglycemia in patients without Diabetes

Hypoglycemia-associated autonomic Failure

• Caused by long standing DM (>5 years) and previous episodes of recurrent SEVERE hypoglycemia
• This causes blunting of catecholamines effects & threshold of their secretion

Diabetic Foot

• Site →most commonly under bony prominences (metatarsal heads)

• Shape → punched out ulcer with undermined border

• Risk is tested for by peripheral sensory neuropathy via a monofilament testing OR by vibrations by a tuning fork

1. SGLT-2 Inhibitors

2. GLP-1 Agonists

1. Microvascular Complications (nephropathy/retinopathy) ⇒ IMPROVE

2. Macrovascular Complications (Stroke/MI) ⇒ NO CHANGE

3. All-Cause mortality ⇒ NO CHANGE/ INCREASED if very intensively controlled (between 6% and 6.5% when compared to recommended target of 7%)

• Patients with hypertension should be screened for DM (via FBG or HbA1C)

• Patients from age 35-70 with no HTN but BMI ≥ 25 should be screened for DM

• Should be ≤7% in most patients with T2DM

• Influenced by fasting glucose & postprandial glucose concentrations
• Fasting Glucose is measure by morning fast sugar (target is 80-130) ⇒ Managed by Basal Insulin
• Postprandial glucose concentrations ⇒ Managed by Rapid-acting Insulin

• Dose should be decreased
• If exercise is within 3 hours of a meal → decrease premeal insulin dose
• If prolonged exercise (marathon) → decrease basal insulin dose

Renal Disorders

Diabetic Kidney Disease (DKD)

• Initially → Hyperfiltration

• Later → decreased GFR & increase in edema & proteinuria

• Evaluation:
• Type 1 DM → Screen for DKD 5 years after dx
• Type 2 DM → Screen for DKD AT TIME of dx
• If Dx is not clear/not decisive, the presence of proliferative diabetic retinopathy (retinal neovascularization) correlates with the presence of DKD.

• Management:
1. Intensive glycemic control
• Target HbA1C ≤ 7%
• SGLT-2 inhibitors are preferred (especially for patients with GFR ≥30)
2. Intensive BP control
• Target <130/80 mmHg
• ACEi/ARBs are preferred
3. General (less effective)
• Smoking Cessation
• Lipid Management

Evaluation of Suspected Polyuria

 

When to do a water deprivation Test?

 

• DI can be undiagnosed for a long period of time due to compensatory thirst mechanisms.
• However, during pregnancy the placenta produces vasopressinases that decrease ADH levels, causing unmasking of the symptoms → DI
• Sometimes, pregnancy can cause sporadic DI, which resolves after delivery & recurs with pregnancies
 

Repro

Secondary Amenorrhea Evaluation

 

• Usually are patients that were on COCs then after cessation, got no period for 1-3 months → REQUIRE EVALUATION

• Amenorrhea is defined as missed menses ≥ 3 months (if regular) or ≥ 6 months (if irregular)

Evaluation of Gynecomastia

 

 

• Soft tissue enlargement without clearly defined, palpable borders or nodules ⇒ pseudogynecomatia
• Management ⇒ Weight loss
 
Unilateral Subareolar firm mass ⇒ Breast Cancer
• Commonly seen in Klinefelter Syndrome, Obesity, and Cirrhosis

Secondary Hypogonadism

• Causes:
• Prolactinomas
• Meds: Opioids, glucocorticoids, and exogenous androgens (withdrawal phase)
• Opioids suppress GnRH & LH secretion → decreased Leydig cells stimulation
• Additional manifestations are osteoporosis, depression, hot flashes, and in women menstrual irregularities
• Hemochromatosis
• Severe/Chronic Illnesses
• Eating Disorders/Severe weight LOSS

• Features: Loss of Libido + ED + Testicular Atrophy

• Labs: Low testosterone with low/normal LH

Virilization of Newborn Female

Virilization of an Adult Females

• Elevated Testosterone with normal DHEAS ⇒ Ovarian Tumor

• Elevated DHEAS ⇒ Adrenal TUmor

Peds

Glucose-6-phosphatase Deficiency

• Von Gierke Diseases

• Caused by impaired conversion of glycogen → glucose

• Presents in children age 3-4 months with hypoglycemia, seizures, lactic acidosis +/- hyperuricemia & hypertriglyceridemia

• “Doll-Facies with round cheeks“ is very buzzy for Von Gierke Disease

Gaucher Disease

• Bone marrow → Anemia/TCP/Leukopenia (any of them)

• HSM

• Bone pain/Osteoporosis/ Avascular Necrosis

• Delayed Puberty & Poor Growth

Phenylketonuria (PKU)

• AR disease caused by phenylalanine hydroxylase deficiency, causing accumulation of phenylalanine and decreased Tyrosine, Dopamine, Melanin, and Catecholamines

• Features: Neurological Injury, Microcephaly, Seizures, Musty odor, Hypopigmentation, Eczema

Infant of mother with DM

Approach to Precocious Puberty

 

 

Management of CPP

• Do MRI to evaluate for hypothalamic/pituitary tumor
• If negative → Idiopathic
• ttt is GnRH therapy

Thyroid

Thyroid Storm

• Usually are patients with undiagnosed Graves with hx of autoimmune diseases (like T1DM)

• Presents as attack of Fever, Seizure, Tachycardia/Arrhythmias, Hypotension, Shock, and Coma following iodine load (in CT scan) or other stressors (surgery, infection, trauma, childbirth)

• Hyperglycemia can also happen due to increased circulating catecholamines

Graves Disease

Euthyroid Sick Syndrome

• Requires no additional labs or TTT

• Just repeat studies after discharge

Struma Ovarri

• Production of thyroid hormone by ovarian teratoma

• Presents in women > 40 years with a pelvic mass + ascites + abdominal pain

Suppurative Thyroiditis

• Euthyroid

• In children + unilateral pain + high-grade fever

Hypothyroidism

• Young healthy male with weight gain despite regular exercise and having a healthy diet + fasting lipids show hyperlipidemia (decrease LDL clearance) and hypertriglyceridemia (decreaes LPL activity).
• Before initiating statins, Thyroid functions must be checked to exclude hypothyroidism, as statin + hypothyroidism ⇒ Myopathy
• If hypothyroidism is present, ttt with levothyroxine improves lipid profile.

• Elderly with decreased concentration, daytime sleepiness, easy fatiguability, forgetfulness, weight gain & decreased appetite, weight loss AND HOARSENESS (due to GAG accumulation in tissue)

• Amenorrhea
• how? ⇒ Low T4 → High TRH (from hypothalamus) → High TSH & PRL → PRL inhibits hypothalamic GnRH → decreased FSH & LH → Anovulatory Amenorrhea

• Recurrent Pregnancy Loss + Subclinical Hypothyroidism (high TSH & normal T4)
• DO → Thyroid Peroxidase antibodies as >90% usually have undiagnosed hashimoto
• TTT → Levothyroxine (even if asymptomatic)

• Congenital Hypothyroidism
• MOST COMMON CAUSE is thyroid dysgenesis
• Asymptomatic at birth → Symptoms develop few weeks after
• Levothyroxine is indicated & no deficits occur if ttt started in neonatal period

• Pregnant Female → Increase dose by 30%

• Females taking COCs, Estrogen Replacement → Increase dose

Approach to Thyroid Nodules

Steps on finding a thyroid nodule:

1. Assess family hx for risk factors

2. Physical examination should assess size, mobility, firmness, and presence of cervical lymph nodes

3. Serum TSH & Thyroid US should be obtained
1. High Risk Features → microcalcifications, increased vascularity, irregular margins

4. If Nodules >1cm with high-risk features OR all noncystic nodules > 2cm OR Hypo-functioning ”Cold” Nodule ⇒ FNA

 

Cold Nodule are very likely to be malignancy

 

Hot Nodules are either Toxic Adenoma, Toxic multinodular goiter (MC after Graves)

• Management → BB + PTU/Methimazole

• TTT → Surgery/Radioiodine ablation

• Complications → Osteoporosis (increased osteoclast activation) → high bone turn over → hypercalcemia & hypercalcuria

Postpartum Thyroiditis

Calcium Homeostasis

Causes of Vitamin D deficiencies

• Increased Catabolism → Anticonvulsants (Carbamazepine, Phenytoin), INH, Rifampin

How to approach Hypercalcemia

1. Is it real hypercalcemia?
1. Measure the ionized portion/albumin. [Albumin only affects the total & doesn’t cause symptoms]

2. Measure PTH levels:
1. High?
1. Primary/Tertiary Hyperparathyroidism (usually <12mg/dL)
2. Familial Hypocalciuric Hypercalcemia
3. Lithium
2. Low?
1. Measure PTHrP, 25-OH vitamin D, and 1,25-OH vitamin D:
1. PTHrP is high with low/normal-low Vitamin D ⇒ Malignancies
2. Vitamin D levels are high ⇒ Sarcoidosis or hypervitaminosis D
3. Calcium level is <12mg/dL ⇒ Thiazides
4. Immobilization (increases osteoclastic resorption ~4 weeks, however, patients with AKI/CKD may develop hypercalcemia in ~4 days)

How to approach Hypocalcemia

 

1. Measure Albumin to confirm true hypocalcemia

2. Exclude Hypomagnesemia, drugs, transfusion (citrate binds ionized calcium, especially in those with hepaic dysfunction due to decreased citrate metabolism)

3. Measure PTH
1. If Increased, measure Vitamin D

Hyperparathyroidism

Milk-Alkali Syndrome

• Caused by excessive intake of calcium (in the form of antacids or OTC minerals for osteoporosis) & absorbable alkali → Hypercalcemia & Metabolic Alkalosis→ Renal VC & decreased GFR

• Risk Factors: CKD + Thiazides/ACEi/NSAIDs

Osteoporosis

• Management:
• First Line: Bisphosphonates (”-dronate”)
• After initiation, DEXA is repeated after 2 years or 1 year if patient is taking steroids
• Side Effects → atypical fractures after prolonged use (this is why it is recommended to be used ≤5 years)
• NOT recommended for patients with renal impairment
• Others:
• Denosumab → Side Effects are Hypocalcemia, infections & skin reactions
• Teriparatide → Useful in severe osteoporosis
• Calcitonin → Reduced pain from fractures

Growth Hormone

Acromegaly Dx Approach:

 

• Management
• Initially → Transsphenoidal Resection of the adenoma
• If unresectable/residual tumor ⇒ Medical ttt is indicated
• Octreotide or GH antagonist (Pegvisomant)

 

Acromegaly HY Features:

• Concentric Cardiomegaly → Diastolic Dysfunction, which may progress to LV dilation & global hypokinesia
• HF is the leading cause of death

Miscellaneous