Autoimmune polyglandular syndromes (APSs) consist of clinical conditions caused by loss of immune tolerance leading to functional defect of multiple endocrine glands and are identified with circulating autoantibodies and lymphocytic infiltration of the affected tissues or organs. This process will consequently end in organ failure (1). There are three main syndromes impairing endocrine system, APS-1, APS-2 and APS-3. Moreover another category occurs in patients having cancer whom are treated with immunoregulatory agents, in which tumor antigens that have steered clear of recognition could be attacked at the expense of activating autoimmunity (2). APS-2 is diagnosed when at least 2 out of 3 manifestations are present in an individual including primary adrenal insufficiency (Addison’s disease), autoimmune thyroid disease-causing Grave disease or hypothyroidism and type 1 diabetes mellitus (T1DM). Other endocrine and non-endocrine manifestations of APS-2 are as following: celiac disease, alopecia, vitiligo, primary hypogonadism, myasthenia gravis, IgA deficiency, pernicious anemia, idiopathic heart block, Stiff-man syndrome, Parkinson’s disease, serositis, dermatitis herpetiformis, idiopathic thrombocytopenia, and hypophysitis (3). It is worth mentioning that this syndrome was first well understood  by Schmidt in 1926, who reported the co-existence  of hypothy-roidism and adrenal insufficiency in patients with lymphocytic infiltration of both the thyroid and adrenal glands and so on; the terms APS-2 and Schmidt Syndrome are used interchangeably (4). In keeping with other autoimmune diseases, APS-2 is also more prevalent in women with the female-to-male ratio of 3-4:1. Prevalence of APS-2 is most happening in the range of 20-40 years of age (1,2,5).

 

A 70-year-old East-Mediterranean woman presented with generalized fatigue that had been going on for two months and had been developing gradually. In addition she had trouble doing the daily chores. The patient had no medical history previously and did not take any drugs either. Patient also complained about loss of appetite and she had lost around 10 kg over the last year. Moreover she had been having trouble with her skin saying she had experienced progressively darkening of the skin all over her body and on her hands and her face to be precise, over the last 10 years. Patient had no history of smoking or usage of either opium or alcohol.
On physical examination, the patient was lethargic and had low blood pressure: 90/60 mmHg with orthostatic hypotension. Hyperpigmentation of the skin (Figures 1 and 2) and mucus membranes were seen (Figures 3 and 4). Thyroid was found smaller than the normal size while palpating. With the impression of thyroid and adrenal issues following laboratory investigations were made.
According to high levels of serum thyroid stimulating hormone (TSH) and low levels of T4, the patient was diagnosed with hypothyroidism (Table 1). Furthermore, low level of Na and high level of K in company with high level of ACTH and low level of Cortisol along with the skin and mucosal manifestations, led us to diagnosis of Primary Adrenal Insufficiency (Table 2).
Adrenal failure was managed with 7.5 mg oral Prednisolone daily and 0.1 mg oral Fludrocortisone daily. She was also treated with levothyroxine 0.1 mg daily as a Hormone replacement therapy due to hypothyroidism.
Further evaluations were made one month later in order to follow Na and K levels.
Since Tuberculosis (TB) is one of the most prevalent causes of adrenal insufficiency, the patient was addressed to take a chest X-ray to evaluate any pulmonary or cardiac problem, which showed no evidence of parenchymal diseases or consolidations in the lung and the heart had normal shape, size and position. More over PPD test was negative as well (Figure 5).

Table 1. Laboratory findings
 

Figure 1&2. Darkening of the skin and hyperpigmentations on hands

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Figure 3 & 4. Hyperpigmantations on the face and around teeth and mucus membranes

Table 2. Following up Na and K

Figure 5. Chest X-Ray for chasing the trace of TB and evaluating any pulmonary or cardiac problem