Approach to Endocrinology PDF

Approach To Endocrinological Diseases Dr. Ahmed Alsolami Associate Professor Dept. of Internal Medicine Background & Physiology Background Medicine is tought in simplified segments. However, integrating the commulative knowledge is the cornerstone for excellent pati...

Approach To Endocrinological Diseases Dr. Ahmed Alsolami Associate Professor Dept. of Internal Medicine Background & Physiology Background Medicine is tought in simplified segments. However, integrating the commulative knowledge is the cornerstone for excellent patient care. Patients mostly do not know which specialty they should book their appointment with when they are faced with a new health problem. While we teach you the symptoms and signs for each disease, you need to reverse-engineer that into a differential diagnosis for each symptom/sign. This is how you start building a comprehensive clinical practice. Endocrine Glands 1.Hypothalamus 8.Pancreas (Islets of Langerhans) 2.Pituitary Gland (Hypophysis) 9.Gonads 1. Anterior Pituitary (Adenohypophysis) 1. Testes (in males) 2. Posterior Pituitary (Neurohypophysis) 2. Ovaries (in females) 3.Pineal Gland 10.Placenta (during pregnancy) 4.Thyroid Gland 11.Additional Hormone-Producing 5.Parathyroid Glands (usually four) Tissues 1. Heart (produces atrial natriuretic 6.Thymus Gland peptide) 7.Adrenal Glands (Suprarenal 2. Kidneys (produce erythropoietin and renin) Glands) 3. Adipose Tissue (produces leptin) 1. Adrenal Cortex 4. Gastrointestinal Tract (produces gastrin, 2. Adrenal Medulla secretin, cholecystokinin, etc.)  Clinical Presentations Untreated Diabetes (Hyperglycemia) Manifestations 1. Polyuria (Excessive Urination): Osmotic diuresis results in the excretion of large volumes of urine. 2. Thirst and Dry Mouth: High blood glucose levels pull water out of cells and tissues into the bloodstream to balance osmotic pressure, causing dehydration and a dry mouth sensation. Also the polyurea participates in causing this symptom. 3. Nocturia (Frequent Nighttime Urination): Increased polyuria due to osmotic diuresis often continues at night, disrupting normal sleep patterns. Untreated Diabetes (Hyperglycemia) Manifestations 4. Tiredness, Fatigue, Lethargy: Cells are unable to efficiently utilize glucose for energy due to insulin deficiency or resistance, leading to cellular starvation despite high blood glucose. 5. Change in Weight (Usually Weight Loss): Lipolysis (fat breakdown) and proteolysis (protein breakdown) result in unintentional weight loss. 6. Blurring of Vision: High glucose levels lead to fluid retention in the lens, altering its shape and impairing its ability to focus, resulting in blurred vision. Untreated Diabetes (Hyperglycemia) Manifestations 7. Pruritus Vulvae and Balanitis (Genital Candidiasis): The warm, moist genital area combined with glucose-rich urine fosters fungal infections, causing itching and inflammation. 8. Nausea: Severe hyperglycemia can lead to delayed gastric emptying (gastroparesis) or ketoacidosis, both of which contribute to nausea. 9. Headache: Loss of fluid and sodium reduces blood volume, potentially affecting brain perfusion and causing pain. Untreated Diabetes (Hyperglycemia) Manifestations 10.Hyperphagia (Increased Hunger, Predilection for Sweet Foods): Cellular glucose starvation stimulates the hypothalamus to signal hunger, even in the presence of high blood glucose levels. 11.Mood Changes, Irritability, Difficulty Concentrating, Apathy: The inability of brain cells to utilize glucose efficiently leads to neurochemical imbalances, affecting mood, cognition, and attention. History Taking Endocrine abnormalities and typical symptoms and signs  Endocrine diseases affect various bodily functions. Symptoms include: Changes in weight, appetite, hair Presenting distribution, pigmentation, sweating, Symptoms in height, menstruation. Galactorrhea, polydipsia, polyuria, Endocrine Diseases lethargy, headaches, loss of libido, erectile dysfunction. Osteoporosis can present with back pain and loss of height (due to vertebral fractures).  Increased appetite with weight loss: Thyrotoxicosis (↑ metabolic activity). Uncontrolled diabetes mellitus (glucose loss in urine). Increased appetite with weight gain: Appetite and Cushing’s syndrome (excessive glucocorticoids). Weight Changes Hypoglycemia, hypothalamic disease. Loss of appetite with weight loss: Adrenal insufficiency, anorexia nervosa, gastrointestinal disease (e.g., malignancy). Loss of appetite with weight gain: Hypothyroidism (↓ metabolic activity).  Diarrhea and increased bowel movements: Bowel Habit Hyperthyroidism, adrenal insufficiency. Changes Constipation: Hypothyroidism, hypercalcemia.  Increased sweating: Hyperthyroidism, Sweating Changes phaeochromocytoma, hypoglycemia, acromegaly. Other causes: Anxiety, menopause.  Hirsutism: Excessive hair growth in women (diagnosis detailed separately). Absence of facial hair in men: Suggests hypogonadism. Hair Distribution Temporal hair recession in women: Changes Indicates androgen excess. Loss of axillary/pubic hair in both sexes: Hypogonadism, hypopituitarism, adrenal insufficiency.  Common in: Hypothyroidism, Addison’s disease, diabetes mellitus. Other causes: Lethargy (Fatigue) Anemia, connective tissue diseases, chronic infections (e.g., HIV, infective endocarditis). Drugs (e.g., sedatives, diuretics), chronic liver disease, renal failure, malignancy, depression.  Hypothyroidism: Coarse, pale, dry skin. Hypoparathyroidism: Dry, scaly skin. Carcinoid syndrome: Flushing of face and neck. Acromegaly: Soft-tissue overgrowth, skin tags. Acanthosis nigricans: Skin and Nail Found in acromegaly, Cushing’s syndrome, insulin resistance (e.g., polycystic ovarian Changes syndrome). Xanthelasmata: Present in diabetes, hypothyroidism. Onycholysis: Common in Graves’ disease. Cushing’s syndrome: Thin skin, purple striae, spontaneous bruising (ecchymoses).  Increased pigmentation: Primary adrenal insufficiency, Cushing’s syndrome, acromegaly. Decreased pigmentation: Pigmentation Hypopituitarism. Changes Vitiligo: Localized depigmentation associated with: Hashimoto’s disease, hypothyroidism, Addison’s disease (autoimmune adrenal insufficiency), other autoimmune conditions.  Tall stature: May reflect growth hormone excess (leading to gigantism), gonadotrophin deficiency, Klinefelter’s syndrome, Stature Changes Marfan’s syndrome, generalized lipodystrophy. Short stature: Endocrine causes discussed later.  Primary or secondary hypogonadism: Hyperprolactinemia, hypopituitarism. Erectile Commonly related to: Endothelial dysfunction (vascular Dysfunction disease), emotional disorders. (Impotence) Other causes: Autonomic neuropathy (e.g., in diabetes mellitus, alcoholism). Spinal cord disease, testicular atrophy.  Caused by hyperprolactinemia (often due to a pituitary adenoma). Galactorrhoea Occurs in up to 80% of women, 30% of men. In men, occurs in normal-appearing male breasts.  Amenorrhea: Failure to menstruate. A. Primary Amenorrhea: Failure to start menstruating by age 17. Causes: 1. Ovarian failure (e.g., Turner’s syndrome). Menstrual Changes 2. Pituitary or hypothalamic disease (e.g., tumor, trauma). (Amenorrhoea) 3. Excess androgen production or systemic diseases: 4. Malabsorption, chronic kidney disease, obesity. 5. Imperforate hymen (apparent primary amenorrhea).  B. Secondary Amenorrhea: Cessation of menstruation for 6+ months. Common causes: Pregnancy, menopause. Menstrual Changes Other causes: Polycystic ovarian syndrome, (Amenorrhoea) hyperprolactinemia, virilizing syndromes. Hypothalamic or pituitary disease. Contraceptive pill use, psychiatric disease. Weight loss, particularly in anorexia nervosa.  Polyuria: Urine output >3 liters/day. Causes include: 1. Diabetes mellitus (excessive glucose filtration). 2. Diabetes insipidus: Inadequate renal water conservation due to: Central antidiuretic hormone (ADH) Polyuria deficiency. Renal insensitivity to ADH. 3. Primary polydipsia (excessive water intake): Causes: Psychogenic, hypothalamic disease, drugs (e.g., chlorpromazine, thioridazine), or simple eccentric behavior. 4. Hypercalcemia. 5. Tubulointerstitial or cystic renal disease.  Thyroid Conditions: Surgery for goiter, partial thyroidectomy, or radio-iodine treatment can lead to Past Medical hypothyroidism. Radiation therapy for thyroid carcinoma may History (Endocrine also result in hypothyroidism. Thyroid surgery may cause Conditions) hypoparathyroidism due to parathyroid damage. Diabetes Mellitus: History of diabetes or hypertension  Thyroid: History of anti-thyroid drugs, thyroid hormone, or radioactive iodine Other Past treatment. Endocrine Surgical History: Treatments Previous adrenal or pituitary surgery may result in reduced function. History of head injury may indicate pituitary or hypopituitary damage.  Treatment: Managed by diet, insulin, or oral hypoglycemic agents. History of Diabetes Assess understanding of: Diabetic diet. Mellitus Blood sugar monitoring with Management glucometer. Adjusting insulin dosage. Eye care Foot care  Assess: Social History Patient’s ability to cope with the disease. Home and work conditions affecting treatment success.  Thyroid conditions or diabetes mellitus Family History may run in families.  Physical Examination  Location: Anterior to larynx and trachea, below the thyroid cartilage. Structure: Isthmus: Narrow, 1.5 cm in size, located Thyroid Gland over the 2nd to 4th tracheal rings. Anatomy Lateral lobes: Each ~4 cm long. Enlargement (Goiter): More common in women (10%) than men (2%). Associated with iodine deficiency.  Normal thyroid may be visible below the cricoid cartilage in thin individuals. Look for goiter: Apparent on inspection, especially with Inspection of neck extension. 80% of goiter patients are euthyroid, 10% Thyroid Gland are hypothyroid, 10% are hyperthyroid. During swallowing: Goiter and thyroglossal cyst will rise. Non-thyroid masses may move but less than the trachea.  Best performed from behind. Assess: Size: Approximate estimation, feel for lower border to rule out retrosternal extension. Shape: Uniform or irregular, nodules? Consistency: Palpation of Normal: Soft. Thyroid Gland Firm: Simple goiter, Hashimoto’s thyroiditis. Stony-hard: Suggests carcinoma or Riedel’s thyroiditis. Tenderness: Possible in thyroiditis or carcinoma. Mobility: Loss of mobility suggests carcinoma.  Percussion: Over manubrium to detect dullness, suggesting retrosternal goiter. Percussion and Auscultation: Listen for bruit indicating Auscultation of increased blood flow (e.g., hyperthyroidism). Thyroid Differential: Carotid bruit or venous hum. Pemberton’s Sign Ask patient to lift arms high. Positive sign: Facial congestion, cyanosis, neck vein distension. Indicates thoracic inlet obstruction from retrosternal goitre or mass.  Excessive thyroid hormone production. Common causes: Graves’ disease (autoimmune). Thyroxine overuse (weight loss Hyperthyroidism purposes). Amiodarone (iodine-rich drug). (Thyrotoxicosis) Symptoms: Tremor, tachycardia, sweating (sympathetic overactivity). Weight loss, anxiety, frightened facies.  Hands: Look for fine tremor (sympathetic overactivity), onycholysis (Plummer’s nails), palmar erythema, warmth, and sweating. Physical Check pulse for tachycardia or atrial fibrillation. Examination in Eyes: Hyperthyroidism Check for exophthalmos (Graves’ disease), chemosis, conjunctivitis, and corneal ulceration. Look for lid retraction (Dalrymple’s sign) and lid lag (von Graefe’s sign).  Thyroid enlargement: Usually diffusely enlarged in Graves’ disease. Presence of thrill in hyperactive Neck and Thyroid in thyroid states (e.g., thyrotoxicosis). Differential diagnoses: Hyperthyroidism Toxic multinodular goiter, solitary nodule, subacute thyroiditis (de Quervain’s). No goiter in elderly patients or those with thyroid hormone overuse.  Deficiency of thyroid hormone due to: Primary thyroid disease or pituitary/hypothalamic failure. Myxedema: Severe form of hypothyroidism with Hypothyroidism mucopolysaccharide accumulation in tissues. Symptoms: Cold intolerance, muscle pain, oedema, constipation, hoarse voice, memory loss, weight gain.  General inspection: Look for mental/physical sluggishness, slow speech, and cool, dry skin. Hands: Physical Check for peripheral cyanosis, hypercarotenaemia (yellowing of Examination in palms), palmar crease pallor (anemia). Hypothyroidism Face: Inspect for periorbital oedema, alopecia, xanthelasmata (hypercholesterolemia). Look for thickened skin, swollen tongue, and slow speech.  Thyroid gland: Goiter due to TSH over secretion in primary hypothyroidism. Exceptions: Iodine deficiency, Hashimoto’s Additional Signs in disease, treated thyrotoxicosis. Hypothyroidism Legs: Test for non-pitting oedema and hung-up reflexes (delayed relaxation phase after contraction). Look for signs of peripheral neuropathy.  Definition: Deficiency of most or all pituitary hormones. Common Causes: Space-occupying lesions, pituitary destruction. Hormone Loss Progression: Growth Hormone: Dwarfism in children, Panhypopituitarism insulin sensitivity in adults. Prolactin: Lactation failure post-delivery. Gonadotrophins: Loss of secondary sexual characteristics, infertility. TSH: Hypothyroidism. ACTH: Hypoadrenalism, reduced adrenal androgen production.  General Inspection in Panhypopituitarism Physical Signs: Short stature (if GH deficiency pre-growth completion). Skin pallor (due to anemia, ACTH deficiency). Fine-wrinkled skin, lack of body hair (gonadotrophin deficiency). Absent Secondary Sexual Characteristics (if gonadotrophin deficiency pre-puberty).  Facial Examination in Panhypopituitarism Facial Features: Multiple wrinkles around the eyes (gonadotrophin deficiency). Hypophysectomy Scars: Transfrontal scars visible; transsphenoidal scars (via upper lip incision) not visible. Ophthalmic Examination: Visual Field Defects: Bitemporal hemianopia from optic chiasm compression. Fundus Examination: Check for optic atrophy.  Cause: Excessive growth hormone, usually from a pituitary adenoma. Growth Hormone Effects: Acromegaly Liver and tissues produce somatomedins. Diabetogenic: Increases hepatic glucose release, anti-insulin effects. Onset: Gradual, with common symptom of headache. Acromegaly Normal  Gigantism: GH hypersecretion before puberty, causing skeletal and soft-tissue Gigantism vs. overgrowth. Acromegaly Acromegaly: GH excess after epiphyseal fusion, leading to soft-tissue and flat- bone enlargement.  Hands: Wide, spade-like shape due to tissue and bone enlargement. Physical Increased sweating, thickened skin. Arms: Examination in Proximal myopathy, possible ulnar nerve Acromegaly thickening. Axillae: - Skin tags (molluscum fibrosum), greasy skin, and acanthosis nigricans.  Key Signs: - Large supraorbital ridge (frontal bossing). - Thickened lips, enlarged tongue, prognathism. Facial Examination Ophthalmic Exam: in Acromegaly - Bitemporal hemianopia, optic atrophy, papilledema, possible angioid streaks. Oral Examination: - Splayed, separated teeth with malocclusion.  Neck: Thyroid enlargement. Chest: Coarse body hair, gynaecomastia, Systemic possible cardiomegaly or arrhythmias. Examination in Back: Check for kyphosis. Abdomen: Hepatic, splenic, renal enlargement; Acromegaly possible testicular atrophy. Lower Limbs: Signs of osteoarthritis, foot drop from peroneal nerve entrapment.  Key Disorders: Cushing’s Syndrome: Chronic glucocorticoid excess. Introduction to Addison’s Disease: Adrenocortical hypofunction. Adrenal Disorders Cushing’s Syndrome vs. Cushing’s Disease: Cushing’s Syndrome: Excessive steroid hormone production from any cause. Cushing’s Disease: Pituitary ACTH overproduction specifically.  Steroid Effects: Increased protein catabolism, gluconeogenesis. Pathophysiology of Stimulation of DNA-dependent synthesis of select mRNAs, leading to enzyme production that alters cell Cushing’s function. Characteristics of Steroid Excess: Syndrome Central obesity, moon face, thin limbs. Bruising, pigmentation changes (due to ACTH’s MSH-like activity).  Hands: Physical Skinfold thickness (≥1.8 mm in young women). Standing Inspection: Moonlike facies, central obesity with thin limbs. Examination in Characteristic Signs: Cushing’s Bruising, pigmentation on extensor surfaces. Buffalo hump (inter-scapular fat deposition). Syndrome Proximal myopathy (muscle weakness, potassium loss). Back: Bony tenderness (possible vertebral crush fractures from osteoporosis).  Facial Features: Moon face, plethora, possible acne, and hirsutism. Face and Neck Telangiectasia presence. Examination in Visual and Fundus Examination: Check visual fields for pituitary tumor signs. Cushing’s Syndrome Fundus: Look for optic atrophy, papilledema, hypertensive or diabetic changes. Neck: Supraclavicular fat pads.  Abdominal Examination: Abdominal and Purple striae (≥1 cm wide). Lower Body Striae may also appear on upper arms or inner thighs. Examination in Palpate for adrenal masses, hepatomegaly. Cushing’s Legs: Syndrome Oedema, bruising, poor wound healing.  Definition: Adrenocortical hypofunction with reduced Addison’s Disease glucocorticoid and mineralocorticoid secretion. Common Cause: Autoimmune adrenal disease.  General Appearance: Look for cachexia. Pigmentation: Hyperpigmentation in palmar creases, Physical elbows, gums, buccal mucosa, genital area, and scars. Examination in Associated with compensatory ACTH Addison’s Disease hypersecretion. Vitiligo: Localized hypomelanosis, commonly co-occurs with autoimmune adrenal failure. Blood Pressure in Measurement: Addison’s Disease Check for postural hypotension.  Cushing’s Syndrome: Excess glucocorticoids, central obesity, moon face, skin changes. Look for signs of adrenal carcinoma or Summary of ectopic ACTH if suspected. Adrenal Disorders Addison’s Disease: Adrenocortical insufficiency, hyperpigmentation, postural hypotension. Commonly autoimmune-related, may present with other autoimmune diseases.  Definition: Chronic condition characterized by hyperglycemia due to insulin deficiency (absolute or relative). Introduction to Presentation: Diabetes Mellitus Asymptomatic glycosuria in routine exams. Symptomatic ranging from polyuria to diabetic ketoacidosis. Diabetes Physical Exam (special focus) Examination of the hands Several abnormalities are more common in diabetes: Limited joint mobility (‘cheiroarthropathy’) causes painless stiffness. The inability to extend (to 180°) the metacarpophalangeal or interphalangeal joints of at least one finger bilaterally can be demonstrated in the ‘prayer sign’ Dupuytren’s contracture causes nodules or thickening of the skin and knuckle pads Carpal tunnel syndrome presents with wrist pain radiating into the hand Trigger finger (flexor tenosynovitis) may be present Muscle-wasting/sensory changes may be present in peripheral sensorimotor neuropathy, although this is more common in the lower limbs Diabetes Physical Exam (special focus) Examination of the feet Inspection Sensation Look for evidence of callus This is abnormal in stocking formation on weight-bearing distribution in typical areas, clawing of the toes peripheral sensorimotor (in neuropathy), loss of the neuropathy plantar arch, discoloration of Testing light touch with the skin (ischaemia), monofilaments is sufficient localised infection and for risk assessment; test ulcers other sensation modalities Deformity may be present, (vibration, pain, especially in Charcot proprioception) only when neuroarthropathy neuropathy is being Fungal infection may affect evaluated skin between toes, and nails Reflexes Circulation Ankle reflexes are lost in Peripheral pulses, skin typical sensorimotor temperature and capillary neuropathy refill may be abnormal Test plantar and ankle reflexes  Dehydration: Assess for dehydration due to osmotic diuresis. General Physical Body Habitus: Obesity (common in Type 2 diabetes). Inspection in Weight loss (indicates uncontrolled glycosuria). Diabetes Kussmaul’s Breathing: Present in diabetic ketoacidosis due to fat metabolism increase and ketone production.  Focus: Legs and feet (major physical signs). Skin Inspection: Hairless, atrophic skin (small-vessel vascular disease, ischemia). Lower Limb Ulcers on pressure points (due to ischemia and neuropathy). Examination in Signs of Charcot’s Joint: Deformed joints Diabetes from repeated injuries. Infections: Look for boils, cellulitis, fungal infections. Diabetic Dermopathy: Pigmented scars, linear plaques on shins.  Necrobiosis Lipoidica Diabeticorum: Yellowish central area with red margin, common on shins. Specific Skin May ulcerate if active. Manifestations in Injection Site Changes: Diabetes Fat atrophy or hypertrophy from insulin injections. Muscle wasting in quadriceps (femoral nerve mononeuropathy).  Injection Sites: Palpate for fat atrophy/hypertrophy. Palpation of Lower Peripheral Pulses: Absent pulses, cold extremities indicate peripheral vascular disease. Limbs Capillary Refill Test: Slower refill suggests vascular compromise.  Peripheral Neuropathy: Neurological Loss of sensation, particularly dorsal column loss. Examination of Reflexes and muscle power, Lower Limbs especially proximal (diabetic amyotrophy). Upper Limb and Nail Health: Candida infection in nails. Systemic Blood Pressure: Measure in lying and standing positions (autonomic neuropathy leads to Examinations postural hypotension).  Vision: Retinal disease, temporary vision Facial and disturbance from lens changes. Ophthalmic Eye Signs: Rubeosis (new blood vessels on the Assessment iris - may cause glaucoma). Cataracts due to sorbitol accumulation in the lens.  Types of Retinal Changes: Non-Proliferative: Ischemic damage with dot/blot Diabetic Retinopathy hemorrhages, microaneurysms, and exudates. Proliferative: New vessel formation, risk of vitreous hemorrhage, retinal detachment.  Cranial Nerves 3, 4, and 6: Neurological Commonly affected; diabetic third nerve palsy with pupil sparing. Impact on Cranial Rare Complications: Nerves Rhinocerebral mucormycosis in poorly controlled diabetes.  Ear Examination: Malignant otitis externa (Pseudomonas infection, may cause facial nerve palsy). Oral Health: Ears, Mouth, and Look for Candida infection in the mouth. Neck Examination Neck and Shoulders: Carotid artery assessment for vascular disease. Acanthosis nigricans indicating insulin resistance.  Hepatomegaly: Abdominal Examination Fatty infiltration