Diagnosis

Cushings disease

A pituitary corticotroph adenoma causing chronic over-secretion of adrenocorticotropic hormone (ACTH) resulting in endogenous Cushing syndrome (hypercortisolism).

Etiology

Cause [82s][3bt][3in]

Pathophysiology [788]

  1. Functional adenoma in the anterior pituitary

  2. Increased adrenocorticotropic hormone (ACTH) production from the

  3. Excess cortisol release from the adrenal glands (bilateral adrenal hyperplasia)

  4. Cortisol --> glucocorticoid:

    • weight gain, striae, acne, flushing, poor wound healing, lower limb edema, fatigue, impaired glucose tolerance, osteoporosis, hyperpigmentation, mood/memory changes, amenorrhea, hirsutism, decreased sexual drive, or frequent infections

  5. Cortisol in high concentrations --> mineralocorticoid activity --> activate renin-angiotensin-aldosterone system --> may cause:

    • hypertension

    • hypokalemia

Complications [788]

Epidemiology

Incidence per 100.000 [3bt][h62][mtv][abt]

Epidemiology chart for Incidence

Symptoms & findings

Symptoms

Acne, Amenorrhea, Buffalo hump, Decreased libido, Depression, Hirsutism, Hyperpigmentation, Hypertension, Impaired memory, Moon face, Muscle atrophy, Muscle weakness, Obesity, Stria, Weight gain

Clinical findings

Elevated Cortisol, Elevated Hematocrit, Elevated Hemoglobin, Hyperglycemia, Osteoporosis, Polycythemia

Anamneses

Diabetes mellitus

Localized findings

Rash
Radiates
CaputCollumThoraxAbdomenArmBackLower body
Distribution
MultipleSymmetricLocalizedGeneralized
Lesion type
PapuleNoduleSeborrheaComedone
Color
RedBlackWhite
Associated symptom
ItchBleedingDischargeSwelling

Approach

Treatment

  1. Transsphenoidal pituitary surgery -> resection of the tumor [aay][yhi]

  2. After successful pituitary surgery -> hydrocortisone replacement

  3. If relapse or when surgery not possible:

    • Medical treatment:

      • Inhibitors of ACTH: Pasireotide (somatostatin receptor ligand)

      • Adrenal inhibition: Ketoconazole, Metyrapone, Mitotane and Etomidate

      • Glucocorticoid receptor blockade: Mifepristone

      • Treatment of comorbidities (hypertension, diabetes, obesity, dyslipidemia)

    • Bilateral adrenalectomy

    • Pituitary radiotherapy

Differential diagnoses

Alcoholism, Cancer origo incerta, Cushing syndrome, Depression, Lipodystrophy Syndromes, Obesity, Primary Generalized Glucocorticoid Resistance Syndrome

References

[1] Chang M, Yang C, Bao X, Wang R. Genetic and Epigenetic Causes of Pituitary Adenomas. Front Endocrinol (Lausanne). 2021 Jan 26;11:596554.

[2] Colao A, Boscaro M, Ferone D, Casanueva FF. Managing Cushing's disease: the state of the art. Endocrine. 2014 Sep;47(1):9-20.

[3] Lindholm J, Juul S, Jørgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, Hagen C, Jørgensen J, Kosteljanetz M, Kristensen L, Laurberg P, Schmidt K, Weeke J. Incidence and late prognosis of cushing's syndrome: a population-based study. J Clin Endocrinol Metab. 2001 Jan;86(1):117-23.

[4] Kairys N, Anastasopoulou C, Schwell A. Cushing Disease. [Updated 2023 Feb 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448184/

[5] Etxabe J, Vazquez JA. Morbidity and mortality in Cushing's disease: an epidemiological approach. Clin Endocrinol (Oxf). 1994 Apr;40(4):479-84.

[6] Giuffrida G, Crisafulli S, Ferraù F, Fontana A, Alessi Y, Calapai F, Ragonese M, Luxi N, Cannavò S, Trifirò G. Global Cushing's disease epidemiology: a systematic review and meta-analysis of observational studies. J Endocrinol Invest. 2022 Jun;45(6):1235-1246.

[7] Broder MS, Neary MP, Chang E, Cherepanov D, Ludlam WH. Incidence of Cushing's syndrome and Cushing's disease in commercially-insured patients <65 years old in the United States. Pituitary. 2015 Jun;18(3):283-9.

[8] https://emedicine.medscape.com/article/2233083

[9] Uum SV, Hurry M, Petrella R, Koch C, Dranitsaris G, Lacroix A. Management of patients with Cushing's disease: a Canadian cost of illness analysis. J Popul Ther Clin Pharmacol. 2014;21(3):e508-17.

[10] Hakami OA, Ahmed S, Karavitaki N. Epidemiology and mortality of Cushing's syndrome. Best Pract Res Clin Endocrinol Metab. 2021 Jan;35(1):101521.

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