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| THE CLINICAL PICTURE |
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| Year : 2022 | Volume
: 9
| Issue : 3 | Page : 234-235 |
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Ectopic Cushing syndrome presenting as hyperpigmentation
Pooja Arora, Sinu Rose Mathachan
Department of Dermatology, Venereology, and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi, India
| Date of Submission | 04-Mar-2021 |
| Date of Decision | 20-May-2021 |
| Date of Acceptance | 11-Jul-2021 |
| Date of Web Publication | 30-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
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/pigmentinternational.pigmentinternational_
How to cite this article:
Arora P, Mathachan SR. Ectopic Cushing syndrome presenting as hyperpigmentation. Pigment Int 2022;9:234-5 |
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.
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 | Figure 2 Oral cavity showing discrete as well as confluent greyish brown pigmentation over both buccal mucosa and the hard palate.
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 | Figure 3 Dorsal view of the right hand showing longitudinal melanonychia and diffuse pigmentation of nails along with hyperpigmented nail folds and knuckles.
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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×).
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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
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | 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.  |
| 2. | Shekhar S, Dharmshaktu P. On the palms of his hands: ACTH-induced hyperpigmentation. Am J Med 2018;131:144-5. |
| 3. | Koppers LE, Palumbo PJ. Pigmentation and the endocrinologist. Med Clin North Am 1972;56:1041-9. |
| 4. | Benner BJ, Alsma J, Feelders RA. Hyponatraemia and hyperpigmentation in primary adrenal insufficiency. BMJ Case Rep 2019;12:e227200. |
| 5. | Lause M, Kamboj A, Fernandez Faith E. Dermatologic manifestations of endocrine disorders. Transl Pediatr 2017;6:300-12. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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