Disease Correlation

Understanding the correlation between specific endocrine disorders and their characteristic laboratory findings is crucial for accurate diagnosis and effective management

Pituitary Disorders

Acromegaly/Gigantism

• Definition
  • Acromegaly: Chronic disorder resulting from excessive secretion of growth hormone (GH) in adults, leading to gradual enlargement of the bones of the hands, feet, and face
  • Gigantism: Excessive GH secretion before the closure of epiphyseal plates in children, leading to excessive linear growth
• Etiology
  • Pituitary adenoma: Most common cause (GH-secreting tumor)
  • Ectopic GH secretion: Rare
• Laboratory Findings
  • Elevated GH levels: Random GH levels are often elevated, but single measurements are unreliable due to pulsatile secretion
  • Elevated Insulin-Like Growth Factor 1 (IGF-1): Provides a more stable measure of GH activity
  • Lack of GH suppression after glucose load: Failure of GH to suppress to < 1 ng/mL during an oral glucose suppression test
  • Pituitary adenoma: Confirmed by imaging studies (MRI)
• Disease State Correlation
  • Symptoms: Enlargement of hands, feet, and facial features; joint pain; excessive sweating; headaches; visual field defects; glucose intolerance; hypertension; sleep apnea
  • Increased risk of cardiovascular disease, diabetes mellitus, and colon cancer
• Clinical Significance
  • Early diagnosis and treatment are essential to prevent long-term complications
  • Treatment options include surgery, radiation therapy, and medications (e.g., somatostatin analogs, GH receptor antagonists)

Cushing’s Disease

• Definition
  • Specific form of Cushing’s syndrome caused by a pituitary adenoma that secretes excessive adrenocorticotropic hormone (ACTH), leading to overproduction of cortisol by the adrenal glands
• Etiology
  • Pituitary adenoma: ACTH-secreting tumor
• Laboratory Findings
  • Elevated cortisol levels: Increased 24-hour urine free cortisol excretion
  • Elevated late-night salivary cortisol: Loss of diurnal variation in cortisol secretion
  • Elevated ACTH levels: Usually normal or slightly elevated
  • Lack of cortisol suppression with low-dose dexamethasone: Failure to suppress cortisol to < 1.8 μg/dL after a low-dose dexamethasone suppression test
  • Suppression of cortisol with high-dose dexamethasone: Cortisol suppression by ≥ 50% after a high-dose dexamethasone suppression test (helps differentiate from ectopic ACTH secretion)
  • Pituitary adenoma: Confirmed by imaging studies (MRI)
• Disease State Correlation
  • Symptoms: Weight gain, moon face, buffalo hump, hypertension, muscle weakness, skin changes (e.g., striae, easy bruising), glucose intolerance, osteoporosis
  • Increased risk of infections and cardiovascular disease
• Clinical Significance
  • Early diagnosis and treatment are essential to prevent long-term complications
  • Treatment typically involves surgical removal of the pituitary adenoma

Hypopituitarism

• Definition
  • Condition characterized by partial or complete loss of pituitary hormone function
• Etiology
  • Pituitary adenoma or tumor: Mass effect on normal pituitary tissue
  • Surgery or radiation therapy: Treatment for pituitary tumors
  • Pituitary infarction: Sheehan’s syndrome (postpartum pituitary necrosis)
  • Traumatic brain injury
  • Infections or inflammatory conditions
• Laboratory Findings
  • Deficiencies in one or more pituitary hormones: GH, ACTH, TSH, LH, FSH, prolactin
  • Low levels of target gland hormones: Cortisol, thyroid hormones, sex hormones
  • Abnormal responses to stimulation tests: Impaired GH response to insulin tolerance test, impaired cortisol response to ACTH stimulation test
• Disease State Correlation
  • Symptoms depend on which hormones are deficient
  • Growth hormone deficiency: Short stature in children, fatigue, decreased muscle mass, and increased body fat in adults
  • Adrenal insufficiency: Fatigue, weakness, weight loss, hypotension
  • Hypothyroidism: Fatigue, weight gain, cold intolerance
  • Hypogonadism: Infertility, sexual dysfunction, decreased libido
  • Diabetes insipidus: Polyuria and polydipsia due to ADH deficiency
• Clinical Significance
  • Hormone replacement therapy is essential to treat hormone deficiencies and prevent complications

Thyroid Disorders

Hyperthyroidism

• Definition
  • Condition characterized by excessive thyroid hormone production and hypermetabolism
• Etiology
  • Graves’ disease: Autoimmune disorder with thyroid-stimulating antibodies
  • Toxic nodular goiter: Overactive thyroid nodules
  • Thyroiditis: Inflammation of the thyroid gland
  • Excessive thyroid hormone intake
• Laboratory Findings
  • Suppressed TSH: Often < 0.1 μIU/mL
  • Elevated free T4 and/or free T3
  • Elevated TSH receptor antibody (TRAb): Specific for Graves’ disease
  • Radioactive iodine uptake scan: Increased uptake in Graves’ disease and toxic nodular goiter
• Disease State Correlation
  • Symptoms: Weight loss, anxiety, irritability, palpitations, heat intolerance, sweating, tremor, goiter, and exophthalmos (bulging eyes) in Graves’ disease
  • Increased risk of atrial fibrillation and osteoporosis
• Clinical Significance
  • Treatment options include antithyroid medications, radioactive iodine therapy, and surgery

Hypothyroidism

• Definition
  • Condition characterized by insufficient thyroid hormone production and hypometabolism
• Etiology
  • Hashimoto’s thyroiditis: Autoimmune destruction of the thyroid gland
  • Iodine deficiency: Rare in developed countries
  • Thyroidectomy: Surgical removal of the thyroid gland
  • Radiation therapy: Damage to the thyroid gland
  • Central hypothyroidism: Pituitary or hypothalamic dysfunction
• Laboratory Findings
  • Elevated TSH: > 4.0 μIU/mL (primary hypothyroidism)
  • Low free T4
  • Elevated thyroid peroxidase antibody (TPO Ab): Suggests Hashimoto’s thyroiditis
  • Low or normal TSH: Central hypothyroidism
• Disease State Correlation
  • Symptoms: Fatigue, weight gain, constipation, cold intolerance, dry skin, hair loss, and cognitive impairment
  • Severe hypothyroidism can lead to myxedema coma, a life-threatening condition
• Clinical Significance
  • Treatment involves thyroid hormone replacement therapy with levothyroxine

Adrenal Disorders

Cushing’s Syndrome

• Definition
  • Condition characterized by chronic exposure to excessive glucocorticoids (cortisol)
• Etiology
  • Exogenous glucocorticoids: Most common cause (iatrogenic Cushing’s syndrome)
  • Cushing’s disease: Pituitary adenoma causing excessive ACTH production
  • Ectopic ACTH syndrome: ACTH-secreting tumor outside the pituitary (e.g., small cell lung cancer)
  • Adrenal tumor: Cortisol-secreting tumor in the adrenal gland
• Laboratory Findings
  • Elevated cortisol levels: Increased 24-hour urine free cortisol excretion
  • Elevated late-night salivary cortisol: Loss of diurnal variation in cortisol secretion
  • Elevated fasting glucose: Increased glucose levels due to insulin resistance
  • ACTH levels: Variable depending on the cause
    • Elevated in Cushing’s disease and ectopic ACTH syndrome
    • Suppressed in adrenal tumors and exogenous glucocorticoid use
  • Abnormal responses to dexamethasone suppression tests
• Disease State Correlation
  • Symptoms: Weight gain, moon face, buffalo hump, hypertension, muscle weakness, skin changes (e.g., striae, easy bruising), glucose intolerance, osteoporosis
  • Increased risk of infections and cardiovascular disease
• Clinical Significance
  • Treatment depends on the underlying cause and may involve surgery, radiation therapy, or medications

Addison’s Disease (Primary Adrenal Insufficiency)

• Definition
  • Condition characterized by the destruction or dysfunction of the adrenal glands, leading to deficient cortisol and aldosterone production
• Etiology
  • Autoimmune adrenalitis: Most common cause
  • Infections: Tuberculosis, fungal infections
  • Hemorrhage: Adrenal hemorrhage
  • Metastatic cancer
• Laboratory Findings
  • Low cortisol levels: Decreased morning cortisol
  • Elevated ACTH levels: Lack of negative feedback from cortisol
  • Low aldosterone levels: Decreased serum aldosterone
  • Elevated plasma renin activity (PRA): Indicates volume depletion
  • Hyponatremia: Low serum sodium
  • Hyperkalemia: High serum potassium
  • Abnormal response to ACTH stimulation test: Minimal or no increase in cortisol levels after ACTH administration
• Disease State Correlation
  • Symptoms: Fatigue, weakness, weight loss, anorexia, nausea, vomiting, abdominal pain, hyperpigmentation, hypotension, and salt craving
  • Adrenal crisis: A life-threatening condition characterized by severe hypotension, shock, and electrolyte imbalances
• Clinical Significance
  • Treatment involves lifelong hormone replacement therapy with glucocorticoids (e.g., hydrocortisone) and mineralocorticoids (e.g., fludrocortisone)

Pheochromocytoma

• Definition
  • Rare tumor of the adrenal medulla that produces excessive catecholamines (epinephrine and norepinephrine)
• Etiology
  • Sporadic: Most common
  • Genetic syndromes: Multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau (VHL) disease
• Laboratory Findings
  • Elevated plasma metanephrines: Highly sensitive and specific
  • Elevated 24-hour urine metanephrines: Alternative to plasma metanephrines
  • Elevated plasma catecholamines: Less sensitive and specific than metanephrines
  • Imaging studies (CT or MRI): To localize the tumor
• Disease State Correlation
  • Symptoms: Hypertension (often paroxysmal), palpitations, sweating, headaches, anxiety, and tremor
  • Increased risk of cardiovascular complications, such as stroke and myocardial infarction
• Clinical Significance
  • Diagnosis is essential to prevent life-threatening complications
  • Treatment involves surgical removal of the tumor after adequate alpha-adrenergic blockade

Parathyroid Disorders

Primary Hyperparathyroidism

• Definition
  • Condition characterized by excessive secretion of parathyroid hormone (PTH), leading to hypercalcemia
• Etiology
  • Parathyroid adenoma: Most common cause
  • Parathyroid hyperplasia: Enlargement of all four parathyroid glands
  • Parathyroid carcinoma: Rare
• Laboratory Findings
  • Elevated serum calcium: Often > 10.5 mg/dL
  • Elevated PTH levels: Inappropriately normal or elevated in the presence of hypercalcemia
  • Low serum phosphate: Due to increased renal excretion of phosphate
  • Elevated 24-hour urine calcium excretion: May be used to assess severity
  • Vitamin D levels: May be low or normal
• Disease State Correlation
  • Symptoms: Often asymptomatic
  • Hypercalcemia symptoms: Bone pain, kidney stones, abdominal pain, constipation, fatigue, and cognitive impairment
  • Complications: Osteoporosis, kidney stones, and cardiovascular disease
• Clinical Significance
  • Treatment may involve surgical removal of the affected parathyroid gland(s)

Hypoparathyroidism

• Definition
  • Condition characterized by deficient secretion of parathyroid hormone (PTH), leading to hypocalcemia
• Etiology
  • Surgical removal of the parathyroid glands: Most common cause
  • Autoimmune destruction of the parathyroid glands
  • Genetic disorders: DiGeorge syndrome
  • Magnesium deficiency: Can impair PTH secretion
• Laboratory Findings
  • Low serum calcium: Often < 8.5 mg/dL
  • Low PTH levels: Inappropriately low in the presence of hypocalcemia
  • Elevated serum phosphate: Due to decreased renal excretion of phosphate
  • Vitamin D levels: May be low or normal
• Disease State Correlation
  • Symptoms: Muscle cramps, tetany, paresthesias (tingling), seizures, and cognitive impairment
  • Severe hypocalcemia can lead to life-threatening cardiac arrhythmias
• Clinical Significance
  • Treatment involves calcium and vitamin D supplementation

Gonadal Disorders

Hypogonadism in Males

• Definition
  • Condition characterized by deficient testosterone production and impaired sperm production
• Types
  • Primary hypogonadism: Testicular failure
  • Secondary hypogonadism: Pituitary or hypothalamic dysfunction
• Etiology
  • Klinefelter syndrome: Genetic disorder (XXY)
  • Testicular trauma or infection
  • Aging: Age-related decline in testosterone production
  • Pituitary or hypothalamic tumors
  • Medications: Anabolic steroids, opioids
• Laboratory Findings
  • Low serum testosterone: Below the normal range for age
  • Elevated LH and FSH: Primary hypogonadism
  • Low or normal LH and FSH: Secondary hypogonadism
  • Semen analysis: May show decreased sperm count and motility
• Disease State Correlation
  • Symptoms: Decreased libido, erectile dysfunction, fatigue, decreased muscle mass, increased body fat, and osteoporosis
• Clinical Significance
  • Treatment may involve testosterone replacement therapy

Polycystic Ovary Syndrome (PCOS)

• Definition
  • Common hormonal disorder affecting women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries
• Etiology
  • Complex interplay of genetic and environmental factors
  • Insulin resistance and hyperinsulinemia play a central role
• Laboratory Findings
  • Elevated serum testosterone: May be mildly elevated
  • Elevated LH/FSH ratio: Often > 2:1
  • Elevated androstenedione and DHEA-S: Adrenal androgens
  • Insulin resistance: Elevated fasting insulin and glucose levels
  • Lipid abnormalities: Elevated triglycerides and low HDL cholesterol
  • Pelvic ultrasound: Polycystic ovaries
• Disease State Correlation
  • Symptoms: Hirsutism, acne, menstrual irregularities, infertility, and obesity
  • Increased risk of type 2 diabetes, cardiovascular disease, and endometrial cancer
• Clinical Significance
  • Management involves lifestyle modifications (diet, exercise), medications to regulate menstrual cycles, and fertility treatments

Key Terms

• Pituitary Adenoma: A tumor of the pituitary gland
• Ectopic ACTH Secretion: ACTH production by a non-pituitary tumor
• Adrenal Insufficiency: A condition in which the adrenal glands do not produce enough cortisol
• Hyperthyroidism: A condition in which the thyroid gland produces too much thyroid hormone
• Hypothyroidism: A condition in which the thyroid gland does not produce enough thyroid hormone
• Pheochromocytoma: A tumor of the adrenal medulla that produces excessive catecholamines
• Hyperparathyroidism: A condition in which the parathyroid glands produce too much parathyroid hormone
• Hypoparathyroidism: A condition in which the parathyroid glands do not produce enough parathyroid hormone
• Hypogonadism: A condition in which the gonads do not produce enough sex hormones
• Polycystic Ovary Syndrome (PCOS): A common hormonal disorder affecting women of reproductive age
• Testosterone: The primary male sex hormone
• Estradiol: The primary female sex hormone
• Progesterone: A female sex hormone involved in the menstrual cycle and pregnancy
• Insulin: A hormone produced by the pancreas that regulates blood sugar levels
• C-Peptide: A byproduct of insulin production
• Human Chorionic Gonadotropin (hCG): A hormone produced during pregnancy
• Laboratory Findings: The results of laboratory tests
• Disease State Correlation: The relationship between specific endocrine disorders and their characteristic laboratory findings
• Clinical Significance: The importance of early diagnosis and treatment to prevent long-term complications
• Treatment Options: The various medical interventions used to manage endocrine disorders