Skin atrophy is a common feature of Cushing’s syndrome (CS), a hypercortisol state, with multiple studies reporting radiographic evidence of reduced skin thickness in this condition1,2.
Measurement of skin thickness on the dorsal aspect of the 2nd or 3rd proximal phalanges on the non-dominant hand by using ECG calipers to pinch together a fold of skin has also been reported to assess skin atrophy in CS, with thickness less than 18 mm correlating strongly with CS3,4; the minimal subcutaneous fat at this location allows for a more accurate measurement of skin thickness.
However, caution should be exercised in interpreting the results of this study. Specifically, some overlap was observed between normal controls and patients with CS. In addition, the study population was limited to women of reproductive age presenting with oligomenorrhea and hirsutism for at least 2 years, a subset of patients that may account for only 40% of cases with CS5,6. Further studies are clearly needed to determine the clinical utility of the skin-fold test in patients suspected of CS.
- Sheppard RH, Meema HE. Skin thickness in endocrine disease. A roentgenographic study. Ann Intern Med 1967;66:531-9.
- Ferguson JK, Donald RA, Weston TS, et al. Skin thickness in patients with acromegaly and Cushing’s syndrome and response to treatment. Clin Endocrinol (Oxf) 1983;18:347-53.
- Corenblum B, Kwan T, Gee S, et al. Bedside assessment of skin-fold thickness: A useful measurement for distinguishing Cushing’s disease from other causes of hirsutism and oligomenorrhea. Arch Intern Med. 1994;154:777-781.
- Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndrome. N Engl J Med 2017;376:1451-9.
- Lindholm J, Juul S, Jorgensen JOL, et al: Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab 2001;86:117–123.
- Lado-Abeal J, Rodriguez-Arnao J, Newell-Price JD, et al. Menstrual abnormalities in women with Cushing’s disease are correlated with hypercortisolemia rather than raised circulating androgen levels. J Clin Endocrinol Metab. 1998;83:3083-8.
Contributed by Sagar Raju, Medical Student, Harvard Medical School
Polyuria is considered a classic symptom of hypercalcemia and was one of the symptoms described in the first published case of hyperparathyroidism (1). Several potential mechanisms may explain this phenomenon.
The calcium sensing receptors (CaSRs) found in the kidney play a major role in volume status due to their expression in the thick ascending loop (TAL) of Henle and the collecting duct. Interestingly, hypercalcemia activates the CaSR in the medullary portion of TAL, causing inhibition of the same cotransporter (Na-K-2Cl) inhibited by furosemide and other loop diuretics (2-4)! Hypercalcemia also inhibits vasopressin action ( therefore urine concentration) by activating CaSR in the collecting duct (5). Lastly, inhibition of Na+-K+ ATPase in the proximal convoluted tubule may further contribute to natriuresis and subsequent polyuria.
Thus, hypercalcemia may lead to polyuria by interfering with the absorption of sodium as well as inhibiting the action of vasopressin. One can’t help but compare its effect to that of a patient with diabetes insipidus taking a loop diuretic! No wonder these patient may suffer from polyuria!
- Goldfarb S, Agus ZS. Mechanism of the polyuria of hypercalcemia. Am J Nephrol. 1984;4:69-76.
- Quamme GA. Effect of hypercalcemia on renal tubular handling of calcium and magnesium. Can J Physiol Pharmacol. 1982;60:1275-80.
- Peterson LN. Vitamin D-induced chronic hypercalcemia inhibits thick ascending limb NaCl reabsorption in vivo. Am J Physiol. 1990;259:122-9.
- Riccardi D, Brown EM. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol. 2010;298:485-99.
- Toka HR, Pollak MR, Houillier P. Calcium sensing in the renal tubule. Physiology (Bethesda). 2015;30:317-26.
Contributed by Michael Hughes, Medical Student, Harvard Medical School
The reported prevalence of AI in patients with liver disease varies widely (30-60%)1. However, there is no consensus on how to define AI in such patients, nor is the methodology for its evaluation standardized. A common criticism is the frequent reliance on total, not free, serum cortisol in cirrhosis which may overestimate the prevalence of AI because cortisol is bound to corticosteroid binding globulin and albumin, commonly found at lower concentrations in cirrhosis. However, even when based on measuring free cortisol, AI is found in 12%-29% of clinically stable cirrhotic patients1.
Secondary AI due to hypothalamic-pituitary dysfunction has been reported in Child-Pugh class A, B, and C patients (42%, 69%, and 80%, respectively)2. The mechanism of AI in cirrhosis is unclear, but low serum cholesterol in cirrhosis leading to lack of substrate for steroidogenesis, and increased levels of circulating endotoxin and pro-inflammatory cytokines impairing the hypothalamic-pituitary-adrenal axis have been postulated1.
- Fede G, Spadaro L, Purrello F. Review: adrenal insufficiency in liver disease. J Liver 2014;3:1.
- Zietz, B, Lock, G, Plach, B, et al. Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis. Eur J Gastroenterol Hepatology 2003;15:495-501.