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Mucocutaneous hyperpigmentation

Published:January 08, 2018DOI:https://doi.org/10.1016/j.ejim.2017.12.015

      1. Indication

      A 43-year-old woman with a 1-year history of 6-kg weight loss and weakness was diagnosed with primary hypothyroidism and started levothyroxine one week before. She presented to the emergency department with a 4-day history of abdominal pain and vomiting. Physical examination revealed BP 80/35 mm Hg, HR 110 bpm, afebrile, slim build and generalized cutaneous hyperpigmentation, especially in the knuckles, the palmar and plantar creases (Fig. 1) and involving gingival mucosa and mucosal surface of lower lip (Fig. 2). Laboratory tests showed decreased serum sodium levels (131 mmol/L) and the remainder was unremarkable. A final test was quickly performed in the emergency room.
      Fig. 1
      Fig. 1Hyperpigmentation, especially in the knuckles and the palmar creases.
      Fig. 2
      Fig. 2Hyperpigmentation involving gingival mucosa and mucosal surface of lower lip.
      What is the diagnosis?

      2. Diagnosis

      Basal serum cortisol was <1.0 μg/dL and basal serum corticotropin was elevated (352 ng/L) and serum cortisol was unaffected after high-dose short Synacthen test, establishing the diagnosis of adrenal crisis – precipitated by treatment with levothyroxine – and primary adrenal insufficiency. Consequently, intravenous hydrocortisone and isotonic saline treatment was initiated without delay and the patient showed rapid improvement. The etiologic study showed positive Anti-TPO antibodies and anti-adrenal antibodies. The final diagnosis was Addison's disease (and Polyglandular Autoimmune Syndrome).
      The prevalence of chronic primary adrenal insufficiency (PAI) is 39–60/million population. Nowadays the most common cause is autoimmune adrenalitis, sometimes accompanied by other autoimmune endocrine deficiencies (autoimmune polyglandular syndromes) [
      • Oelkers W.
      Adrenal insufficiency. Current-concepts.
      ]. An acute onset of abdominal pain, vomiting, hypotension and hyponatremia combined with a long-term history of significant weight loss, weakness and generalized mucocutaneous hyperpigmentation could lead to the suspicion of PAI. Consequently, a precipitating factors must be ruled out, mainly a serious infection or any other major stress. Hyperpigmentation is absent in some patients with PAI and in all patients with secondary and tertiary adrenal insufficiency [
      • Barnett A.H.
      • Espiner E.A.
      • Donald R.A.
      Patients presenting with Addison's disease need not be pigmented.
      ]. In addition, hyperpigmentation can be caused by different drugs. It is important to determine whether the adrenal insufficiency is primary, secondary, or tertiary because it may be due to a disease that has other clinical ramifications. Cortisol secretion is deficient in patients with PAI despite the fact that their ability to secrete corticotropin is intact. The diagnosis of autoimmune PAI is based upon the presence of associated autoimmune disorders and the exclusion of other causes like infectious, hemorrhagic, or metastatic causes. Adrenal crisis is a life-threatening emergency that requires immediate treatment. The goal of therapy is treatment of hypotension and reversal of electrolyte abnormalities and of cortisol deficiency. It is essential that treatment of patients who present in possible adrenal crisis not be delayed while diagnostic tests are performed [
      • Bornstein S.R.
      • Allolio B.
      • Arlt W.
      • et al.
      Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline.
      ].

      Conflicts of interest

      None.

      References

        • Oelkers W.
        Adrenal insufficiency. Current-concepts.
        N Engl J Med. 1996; 335: 1206-1212
        • Barnett A.H.
        • Espiner E.A.
        • Donald R.A.
        Patients presenting with Addison's disease need not be pigmented.
        Postgrad Med J. 1982; 58: 690
        • Bornstein S.R.
        • Allolio B.
        • Arlt W.
        • et al.
        Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline.
        J Clin Endocrinol Metab. 2016; 101: 364