Acromegaly differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Overview

Acromegaly must be differentiated from other diseases that cause acral features like skin thickening and linear bone growth. These diseases such as Marfan syndrome, precocious puberty, prolactinoma, and pachydermoperiostosis.

Differentiating acromegaly from other Diseases

• Acromegaly must be differentiated from other diseases that cause acral features like skin thickening and linear bone growth. These diseases such as Marfan syndrome, precocious puberty, prolactinoma, and pachydermoperiostosis.

Differential Diagnosis	Similar Features	Differentiating Features
Prolactinoma	On physical examination, prolactinoma demonstrates visual field defects and diplopia as acromegaly. On symptoms, prolactinoma patients complain of a headache as the acromegaly.	On physical examination, prolactinoma demonstrates hydrocephalus that distinguishes it from acromegaly. On symptoms, patients with prolactinoma may show cerebrospinal fluid rhinorrhea. On laboratory tests, prolactinoma has a high level of prolactin that distinguishes it from acromegaly.
Marfan syndrome	On physical examination, Marfan syndrome has demonstrated cardiac manifestations as the acromegaly. On physical examination, Marfan syndrome demonstrates excess linear bone growth like acromegaly.	On physical examination, Marfan syndrome patients have small jaws that distinguish it from acromegaly. Patients with Marfan syndrome have arachnodactyly with positive thumb and wrist signs.
Precocious puberty	On physical examination, excess linear bone growth is noticed like the acromegaly.	On laboratory diagnosis, precocious puberty has demonstrated high levels of FSH, LH, and testosterone that distinguish it from acromegaly.
Pachydermoperiostosis (Primary hypertrophic osteoarthropathy)	On physical examination, pachydermoperiostosis demonstrates thickening of skin and scalp, clubbing and arthritis like acromegaly.	On laboratory findings, pachydermoperiostosis has low level of the serum IGF1 which distinguishes it from acromegaly.

Less common differentials Acromegaly should also be differentiated from other causes of hyperprolactinemia that may present as galactorrhea, amenorrhea, (in females) and infertility (in both males and females) including:

• Physiological:
  • Normal pregnancy
• Pathological:
  • Pituitary tumors (other than prolactinoma):
    • Somatotroph adenoma: Acromegaly
    • Corticotroph adenoma: Cushing's syndrome
  • Suprasellar tumors (tumors present in the region of the pituitary stalk)
  • Hypothyroidism
  • Chronic renal failure
  • Liver disease
    • Cirrhosis (with or without encephalopathy)
    • Viral hepatitis (with encephalopathy)
  • Seizure disorder
• Medication-induced:
  • Antipsychotic medications:
    • Haloperidol
    • Risperidone
  • Antiemetic medications:
    • Metoclopramide
    • Domperidone
  • Antihypertensive medications:
    • Methyldopa
    • Verapamil

Disease	Clinical Findings	Laboratory findings	Management
Somatotroph adenoma: Acromegaly	Clinical features of acromegaly are due to high level of human growth hormone (hGH): Soft tissue swelling of the hands and feet Brow and lower jaw protrusion Enlarged hands Enlarged feet Arthritis and carpal tunnel syndrome Increase in teeth spacing Macroglossia (enlarged tongue) Heart failure Kidney failure Compression of the optic chiasm leading to loss of vision in the outer visual fields (typically bitemporal hemianopia) Headache Diabetes mellitus Hypertension Cardiomegaly	Elevated insulin-like growth factor-1 (IGF-1) levels Elevated growth hormone levels	Medical management: Octreotide Bromocriptine Surgical management: Endonasal transsphenoidal surgery Radiation therapy
Corticotroph adenoma: Cushing's syndrome	Clinical features of Cushing's syndrome are due to increased levels of cortisol: Rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity) Proximal muscle weakness A round face often referred to as a "moon face" Excess sweating Headache The excess cortisol may also affect other endocrine systems and cause, for example: Insomnia Reduced libido Impotence Amenorrhea Infertility Patients frequently suffer various psychological disturbances, ranging from euphoria to psychosis. Depression and anxiety are also common.	Dexamethasone suppression test 24 hour urinary measurement of cortisol	Medical management: Pasireotide Cabergoline Ketoconazole Metyrapone Mitotane Mifepristone Surgical management: Transsphenoidal pituitary resection
Hypothyroidism	Clinical features of hypothyroidism are due to deficiency of thyroxine: Fatigue Cold intolerance Decreased sweating Hypothermia Coarse skin Weight gain Hoarseness Goiter Fullness in the throat and neck Depression Emotional lability Attention deficit	Elevated TSH Low T4 Low T3 Elevated anti-thyroid antibodies(anti-TPO)	Levothyroxine
Chronic renal failure	There are no pathognomonic symptoms associated with chronic renal failure. Common non-specific symptoms of chronic renal failure include: Malaise Nausea Unintentional weight loss Pruritus Lower extremity edema Sleep disorders	Urinalysis: Albuminuria Hematuria Pyuria Red cell or white cell casts and crystals Fluid and electrolyte disturbances: Hyponatremia Hyperkalemia Hyperphosphatemia Hyperchloremia Metabolic acidosis Hypocalcemia Endocrine and metabolic disturbances: Hyperuricemia Hypertriglyceridemia Decreased HDL levels Vitamin D deficiency Increased Parathyroid hormone levels Hematologic abnormalities: Normocytic normochromic anemia Lymphocytopenia Leukopenia Thrombocytopenia	Medical management: Blood pressure management Control of blood glucose Protein restriction Management of anemia Management of electrolyte disturbance Dialysis Surgical management Kidney transplant
Liver disease: Cirrhosis	The clinical features of liver cirrhosis are very nonspecific. These include: Right upper quadrant abdominal pain Fever Fatigue and weakness Loss of appetite Diarrhea Nausea and vomiting Weight loss Abdominal pain and bloating when fluid accumulates in the abdomen Itching Menstrual irregularities	Elevated aminotransferases (AST & ALT) Elevated alkaline phosphatase (ALP) Elevated gamma-glutamyl transpeptidase Elevated bilirubin Low albumin Elevated prothrombin time Elevated globulin Hyponatremia Anemia Leukopenia and neutropenia Thrombocytopenia	Medical management: Treatment is usually directed towards the treatment of complications like ascites, esophageal varices, hepatic encephalopathy, hepatorenal syndrome, and spontaneous bacterial peritonitis. Some chronic constitutional symptoms that should be treated include: Pruritis: Cholestyramine is the drug of choice Hypogonadism: Topical testosterone preparations Osteoporosis: Calcium and vitamin D Pain management: NSAIDS, celecoxib, opioids Nutrition: Adequate caloric and protein intake, and multivitamin supplementation Surgical management: Liver transplantation
Seizure disorder	The clinical features of seizure disorder may include: Change in alertness, orientation and time perception Mood changes, such as unexplainable fear, panic, joy, or laughter Changes in sensation of the skin, usually spreading over the arm, leg, or trunk Vision changes, including seeing flashing lights Rarely, hallucinations (seeing things that aren't there) Falling, loss of muscle control, occurs very suddenly Muscle twitching that may spread up or down an arm or leg Muscle tension or tightening that causes twisting of the body, head, arms, or legs Shaking of the entire body Tasting a bitter or metallic flavor	Electroencephalogram	Medical management: Antiepileptic medications
Medication-induced	Clinical features of hyperprolactinemia after a specific period of regular medication ingestion	Discontinuation of the medication for 3 days and remeasurement of prolactin levels	Change to alternate medication