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Year : 2020  |  Volume : 21  |  Issue : 4  |  Page : 326-328

Addisonian hyperpigmentation in a case of late onset familial glucocorticoid deficiency and dramatic improvement with glucocorticoid supplementation

Department of Dermatology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India

Date of Submission20-Oct-2019
Date of Decision13-Nov-2019
Date of Acceptance26-Apr-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Dr. S Rajasekar
32, KEM Annex Boys Hostel, Parel, Mumbai-12, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_104_19

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Addison's disease is a chronic endocrine disorder in which the adrenal glands do not produce enough steroid hormones mostly both glucocorticoid and mineralocorticoid. Most common causes of primary adrenal insufficiency are due to autoimmune adrenalitis in developed world, and tuberculosis in developing world. Here we present a rare case of primary adrenal insufficiency with addisonian pigmentation secondary to familial glucocorticoid deficiency.

Keywords: Addisionian hyperpigmentation, familial glucocorticoid deficiency, increased adrenocorticotropic hormone, normal renin

How to cite this article:
Mahajan S, Chikhalkar S, Rajasekar S. Addisonian hyperpigmentation in a case of late onset familial glucocorticoid deficiency and dramatic improvement with glucocorticoid supplementation. Indian J Paediatr Dermatol 2020;21:326-8

How to cite this URL:
Mahajan S, Chikhalkar S, Rajasekar S. Addisonian hyperpigmentation in a case of late onset familial glucocorticoid deficiency and dramatic improvement with glucocorticoid supplementation. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Oct 28];21:326-8. Available from: https://www.ijpd.in/text.asp?2020/21/4/326/296840

  Introduction Top

Addison's disease is rare endocrinal disorder that affects 1 in 100,000 people. It is seen in all age groups and affects male and female equally. Addison's disease can present as a life-threatening crisis, because it is frequently unrecognized in its early stages. The basis of Addison's disease has dramatically changed from an infectious cause to autoimmune pathology. However, tuberculosis is still the predominant cause of Addison's disease in developing countries.

The symptoms of Addison's disease begin gradually, chronic worsening fatigue, loss of appetite, generalized weakness, hypotension, and weight loss, generalized hyperpigmentation of skin. Adrenal calcification and enlargement are commonly seen in Addison's disease associated with tuberculosis. The symptoms of Addison's disease progress slowly and are usually ignored, an event of illness can lead to Addisonian crisis. Symptoms of Addisonian crisis are severe vomiting and diarrhoea, which is followed by dehydration, low blood pressure and loss of consciousness. Here we present a rare case of primary adrenal insufficiency with Addisonian pigmentation secondary to familial glucocorticoid deficiency (FGD).

  Case Report Top

A 15-year-old male patient born out of second-degree consanguineous marriage presented to our outpatient department with symptoms of asymptomatic blackening of skin and nails for 2 years. Patient also had easy fatigability, and difficulty in concentration since the same time. There was no family history, history of any drug intake or any other complaints. There was no history of cough or tuberculosis in the family. On examination patient had diffuse hyperpigmentation all over body including oral mucosa, tongue and nails [Figure 1], [Figure 2], [Figure 3], [Figure 4]. The differential diagnoses considered were addisonian pigmentation and vitamin B12 deficiency. The patient had normal vitamin B12 level of 420 pg/ml (160–950(pg/mL). The external genitalia were normal. On investigation patient had increased adrenocorticotropic hormone (ACTH) >1500 pg/ml (normal value is 0–46 pg/ml), low serum cortisol of 1.15 μg/dl (normal value is 5–25 μg/dl) with normal aldosterone and renin levels. Random blood sugar level on admission was 81 mg/dl on admission. The imaging studies of abdomen and chest were normal.
Figure 1: Diffuse pigmentation seen over face

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Figure 2: Pigmentation of the mucosal surface

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Figure 3: Pigmentation of extremities along with nails

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Figure 4: Diffuse pigmentation on the trunk

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Based on the clinical features and investigations patient was diagnosed to have FGD. Genetic study to confirm the diagnosis was not done because of nonaffordability of the tests. Patient was started on tablet prednisolone 5 mg per day from endocrinology department. Within 2 months, the pigmentation reduced considerably and patient felt symptomatically better [Figure 5], [Figure 6], [Figure 7].
Figure 5: Pigmenatation reduced considerably in 2 months of treatment

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Figure 6: Pigmenatation reduced considerably in 2 months of treatment

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Figure 7: Pigmenatation reduced considerably in 2 months of treatment

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  Discussion Top

FGD is a rare autosomal recessive disorder characterized by glucocorticoid deficiency in the absence of mineralocorticoid deficiency, presenting with hypoglycaemia, seizures, hyperpigmentation, recurrent infections and failure to thrive.

Due to the lack of feedback inhibition of the hypothalamus, ACTH levels are raised. Plasma renin activity and aldosterone concentrations are usually normal. The most common initial presenting feature is hyperpigmentation of the skin and mucous membranes, which was the case with our patient. Recurrent hypoglycemia especially during infections or stress is also seen. A positive family history of consanguinity or early unexplained infant deaths can also be present. The most frequent cause of death in FGD is undiagnosed hypoglycemia due to glucocorticoid insufficiency. FGD should be distinguished from other disorders that cause adrenal insufficiency.[1] No family history of tuberculosis with clear chest X-rays and normal imaging studies of adrenal rules out tuberculosis. Serum for 21-hydroxylase autoantibodies for autoimmune adrenal insufficiency and very long chain fatty acids for adrenoleukodystrophy was not done. Adrenoleukodystrophy is not probable due to the absence of neurological involvement.[1] The absence of genital ambiguity with normal 17-OH progesterone rules out congenital adrenal hyperplasia. FGD is classified into 2 types: FGD Type 1 and FGD Type 2. Type 1 is characterized by mutation in ACTH receptor (melanocortin 2 receptor [MC2R]) gene and Type 2 is characterized by a mutation in ACTH accessory protein (melanocortin 2 receptor accessory protein [MRAP]). 25% of FGD cases have mutation in MC2R and only 15%–20% of FGD cases have mutations in MRAP.[2],[3],[4] Around 50% of FGD patients have no identifiable mutation in either gene and this group of patients are referred to as having FGD Type 3. Linkage to chromosome 8 has been found in some families with FGD Type 3, although a specific gene has yet to be identified.[5] Genetic studies would be confirming the diagnosis but was not done. Hence, the diagnosis of FGD is made clinically by low serum cortisol and markedly elevated ACTH levels in presence of normal renin-aldosterone axis.[1] The prognosis is good on early detection and the mainstay of treatment in FGD is the replacement of glucocorticoids.

We report this case because FGD as a cause of addisonian pigmentation is very rare but once the diagnosis is made it is easily treatable. Since, it is an autosomal recessive disorder genetic counselling should also be provided to the patient and their family.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Shivaprasad KS, Dutta D, Jain R, Ghosh S, Mukhopadhyay S, Chowdhury S. Familial glucocorticoid deficiency presenting with generalized hyperpigmentation in adolescence. Report of three siblings. Indian J Endocrinol Metab 2012;16:S382-4.  Back to cited text no. 1
Clark AJ, McLoughlin L, Grossman A. Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet 1993;341:461-2.  Back to cited text no. 2
Al Jneibi F, Hen T, Rajah J, Nair R. Early diagnosis in familial glucocorticoid deficiency. Dermatoendocrinol 2017;9:e1310787.  Back to cited text no. 3
Modan-Moses D, Ben-Zeev B, Hoffmann C, Falik-Zaccai TC, Bental YA, Pinhas-Hamiel O, et al. Unusual presentation of familial glucocorticoid deficiency with a novel MRAP mutation. J Clin Endocrinol Metab 2006;91:3713-7.  Back to cited text no. 4
Chan LF, Clark AJ, Metherell LA. Familial glucocorticoid deficiency: Advances in the molecular understanding of ACTH action. Horm Res 2008;69:75-82.  Back to cited text no. 5


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]


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