Home About us Editorial board Ahead of print Current issue Archives Instructions Submit article Search Subscribe Contacts Login
  • Users Online: 469
  • Home
  • Print this page
  • Email this page

 Table of Contents  
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 234-235

Ectopic Cushing syndrome presenting as hyperpigmentation

Department of Dermatology, Venereology, and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi, India

Date of Submission04-Mar-2021
Date of Decision20-May-2021
Date of Acceptance11-Jul-2021
Date of Web Publication30-Nov-2022

Correspondence Address:
Sinu Rose Mathachan
Senior Resident, Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pigmentinternational.pigmentinternational_

Rights and Permissions

How to cite this article:
Arora P, Mathachan SR. Ectopic Cushing syndrome presenting as hyperpigmentation. Pigment Int 2022;9:234-5

How to cite this URL:
Arora P, Mathachan SR. Ectopic Cushing syndrome presenting as hyperpigmentation. Pigment Int [serial online] 2022 [cited 2023 Mar 26];9:234-5. Available from: https://www.pigmentinternational.com/text.asp?2022/9/3/234/362403

Dear Editor,

A 65-year-old male was referred to our outpatient department of dermatology. He was undergoing workup for chronic cough, breathlessness, recent-onset type 2 diabetes mellitus, and hypertension from the department of medicine. On examination, greyish brown pigmentation over the face and upper chest [Figure 1], on the buccal mucosa, and the hard palate [Figure 2] was present. Longitudinal melanonychia in a few nails [Figure 3] and knuckles hyperpigmentation were also noted.
Figure 1 Face and shoulders of the patient showing greyish brown pigmentation predominantly over the centro facial region.

Click here to view
Figure 2 Oral cavity showing discrete as well as confluent greyish brown pigmentation over both buccal mucosa and the hard palate.

Click here to view
Figure 3 Dorsal view of the right hand showing longitudinal melanonychia and diffuse pigmentation of nails along with hyperpigmented nail folds and knuckles.

Click here to view

High-resolution computed tomography (HRCT) of the chest followed by lung biopsy was advised and the latter revealed small cell carcinoma of the lung [Figure 4]. There was an increase in serum cortisol, 24-hour urine cortisol, and serum adrenocorticotropic hormone (ACTH). Serum cortisol remained high after a 2 mg overnight dexamethasone suppression test and the corticotropin-releasing hormone (CRH) stimulation test was negative.[1] Thereby, a diagnosis of Ectopic Cushing syndrome (ECS), probably secondary to lung malignancy, was made. The patient was referred to the oncology department, and a detailed workup showed extensive stage cancer with metastasis in the liver, and the patient was planned for palliative chemotherapy.
Figure 4 Histopathological examination of Lung biopsy demonstrating small round cell tumor of lung consisting of small, round, ovoid, and spindle-shaped cells with scant cytoplasm, and numerous mitotic figures (H & E 100×).

Click here to view

ACTH plays a potential role in the activation of melanocyte-stimulating hormone receptors, thereby increasing the melanin production resulting in hyperpigmentation.[2] Hyperpigmentation in ECS is caused by an increased production of ACTH and MSH that are generated by the cleavage of proopiomelanocortin (POMC). Both ACTH and MSH have marked promelanogenic effects. MSH and ACTH act on melanocortin receptor type 1 (MC1R) of melanocytes displaying melanogenic and mitogenic effects via cAMP-dependent pathways. Receptor binding increases tyrosinase activity, melanin production, and stimulates dendrite formation. The pigmentation is usually diffuse and deeper in the skin of the exposed areas, scars, areola, palmar creases, knuckles, pressure areas, extensor surfaces, and oral mucosa.[3],[4]

Addison’s disease is the most common reported cause for diffuse hyperpigmentation caused by elevated ACTH. ACTH dependent Cushing’s syndrome, caused by pituitary gland tumors and ectopic ACTH-secreting nonpituitary tumors, and Nelson’s syndrome being other rare causes.[3],[4] A systematic and sequential workup of the patient is essential to distinguish ectopic ACTH production, from that of pituitary origin, the latter being the most common cause for ACTH-dependent Cushing syndrome (80%).[1],[2] The most common ectopic sources for ACTH are small cell lung carcinoma and carcinoid tumors followed by tumors of the thymus and pancreas. This case report highlights hyperpigmentation as the presenting sign of malignancy, which is often missed. Other cutaneous manifestations include cushingoid appearance characterized redistribution of adipose tissue: cheeks (“moon facies”), dorsocervical fat pad (“buffalo hump”), supraclavicular fat pad (thick, short neck), and behind the orbit (exophthalmos), easy bruising, delayed wound healing, “Cigarette paper” skin on the elbows and dorsum of the hands, violaceus skin striae, acanthosis nigricans, hirsutism, steroid acne, and predisposition to superficial dermatophyte and pityrosporon infections.[5]

Through this report, we want to reiterate the importance of paraneoplastic manifestations in the skin as a clue for the early diagnosis of malignancy. Clinicians should keep a high index of suspicion in such cases and carry out detailed malignancy workups.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Sathyakumar S, Paul TV, Asha HS et al. Ectopic cushing syndrome: a 10-year experience from a tertiary care center in southern India. Endocr Pract 2017;23:907-14.  Back to cited text no. 1
Shekhar S, Dharmshaktu P. On the palms of his hands: ACTH-induced hyperpigmentation. Am J Med 2018;131:144-5.  Back to cited text no. 2
Koppers LE, Palumbo PJ. Pigmentation and the endocrinologist. Med Clin North Am 1972;56:1041-9.  Back to cited text no. 3
Benner BJ, Alsma J, Feelders RA. Hyponatraemia and hyperpigmentation in primary adrenal insufficiency. BMJ Case Rep 2019;12:e227200.  Back to cited text no. 4
Lause M, Kamboj A, Fernandez Faith E. Dermatologic manifestations of endocrine disorders. Transl Pediatr 2017;6:300-12.  Back to cited text no. 5


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Article Figures

 Article Access Statistics
    PDF Downloaded46    
    Comments [Add]    

Recommend this journal