Type III Polyglandular Autoimmune Syndrome Clinical Presentation

The hallmark of polyglandular autoimmune syndrome (PAS) III is the absence of adrenal insufficiency. In fact, PAS III is PAS II without adrenocortical involvement (see Neufeld and Blizzard's classification in Background). Once adrenocortical insufficiency develops, such patients are reclassified as having PAS II. The involvement of multiple glands may be apparent at the time of initial presentation, but, more commonly, individual glandular failure develops sequentially. No specific sequence exists by which the individual glandular failures develop.

• The clinical symptoms of PAS III are a constellation of manifestations of endocrine gland failures that comprise the syndrome.
• Autoimmune thyroiditis

  • Autoimmune thyroiditis is the characteristic of all subcategories of PAS III.
  • The presenting symptoms are goiter, those due to hypothyroidism, or both. Occasionally, destruction of the gland early in the process gives rise to the release of thyroid hormones, creating a transient hyperthyroid state (ie, Hashitoxicosis). When this process is complete, hypothyroidism becomes apparent.
  • Fatigue and depression are leading symptoms in many patients with autoimmune thyroiditis. Weight gain, cold intolerance, constipation, dry hair, sluggishness, somnolence, hoarseness, and menorrhagia also are major clinical symptoms.
  • Although some patients report a sensation of tightness in the neck, pain is usually not a prominent symptom. Patients may have a history of other autoimmune conditions such as inflammatory bowel disease, celiac disease, gonadal dysgenesis (Turner syndrome), and hepatitis C.
• Immune-mediated diabetes

  • Classic symptoms of IMD are polyuria, polydipsia, and polyphagia. Polyuria is secondary to osmotic diuresis caused by hyperglycemia. Polydipsia is secondary to hyperosmolality. Polyphagia is probably secondary to deficient glucose utilization in the cells of the hypothalamic ventromedial nuclei.
  • Weight loss despite polyphagia is characteristic.
  • Blurred vision is common and also is secondary to hyperosmolality.
  • Paresthesia in the extremities may be present at presentation, although it is usually reversible with better glycemic control. Paresthesia is thought to be secondary to transient impairment of peripheral sensory nerve function caused by hyperglycemia.
  • Rapid development of insulin deficiency, usually precipitated by infection or other forms of stress, could result in diabetic ketoacidosis (DKA) as the initial presentation of type 1 diabetes mellitus. Abdominal pain, nausea, and vomiting are common in DKA, along with above symptoms. Altered mental status and rapid breathing are symptoms associated with severe DKA.
• Pernicious anemia

  • Usual presenting features include insidious onset of fatigue, weakness, lightheadedness, headache, vertigo, tinnitus, and palpitations secondary to anemia.
  • Vague gastrointestinal symptoms, such as anorexia or diarrhea, may be present. Sore tongue, numbness and tingling in the extremities, and difficulty with balancing may be present at onset or may develop later in the course.
  • Neuropsychiatric manifestations may not parallel symptoms of anemia. In addition to the above neurological symptoms, irritability, memory loss, depression, hallucinations, agitation, suicidal ideation, and sphincter disturbances are recognized manifestations.
• Vitiligo

  • Vitiligo is associated with many autoimmune endocrinopathies. Patients with an early age of onset are less likely to have PAS II or other endocrinopathies.
  • Loss of skin pigmentation in vitiligo has been linked to autoimmune destruction of melanocytes by antityrosinase and antimelanocyte antibodies. The leading symptom is loss of skin pigmentation, which is more noticeable around the mouth, eyes, nose, nipples, umbilicus, or anus. Trauma to the skin results in further loss of pigmentation (Koebner phenomenon).
• Alopecia

  • Autoimmune alopecia (alopecia areata) ranges in severity from (1) small round patches of hair loss that regrow spontaneously to (2) persistent extensive patchy involvement to (3) the loss of all scalp hair (alopecia totalis) or all scalp and body hair including eyelashes, eyebrows, underarm hair, and pubic hair (alopecia universalis).
  • In the latter, absence of eyebrows results in perspiration trickling into the eyes; absence of eyelashes results in little protection from dust and glare. Absence of nasal hairs results in lack of protection in the nostrils or sinuses from foreign particles in the air. Spontaneous remission and recurrence are common.

• Autoimmune thyroiditis

  • Physical findings in autoimmune thyroiditis are goiter, hypothyroidism, or both. The thyroid gland is palpably enlarged in classic goitrous autoimmune thyroiditis (Hashimoto disease). The entire thyroid gland is diffusely enlarged and is firm. The surface of the thyroid gland often is bosselated, that is, characterized by numerous bosses or rounded protuberances.
  • Extrathyroidal signs of autoimmune thyroiditis and hypothyroidism include facial pallor; bradycardia; hypertension; delayed relaxation of deep-tendon reflexes; and nonpitting edema (myxedema) of the skin of the hands, feet, and eyelids.
• Immune-mediated diabetes

  • Dry skin and mucous membranes may be observed secondary to fluid loss associated with osmotic diuresis.
  • Severe dehydration or severe DKA may lead to hypotension.
• Pernicious anemia

  • The most striking physical sign of PA is pallor.
  • Mild scleral icterus may be present secondary to indirect hyperbilirubinemia caused by intramedullary hemolysis.
  • The tongue usually is smooth, raw, and beefy.
  • Systolic flow murmur and tachycardia may be present secondary to anemia.
  • Neurological signs may vary from diminished vibration and joint position sense to gross motor, sensory, and cognitive deficits.
  • A marked discordance may be present between the severity of neurological signs and the degree of anemia (see History).
• Vitiligo

  • Vitiligo is characterized by symmetric areas of complete pigment loss, particularly affecting the periorificial areas and bony prominences.
  • The hairs within the patches of vitiligo often remain pigmented. However, in older lesions, the hairs also become white. Wood-lamp examination reveals more apparent chalky-white areas.
• Alopecia

  • Alopecia areata causes different patterns of hair loss.
  • These include a localized patch of hair loss, a netlike pattern of hair loss, a serpentine pattern of hair loss that covers the periphery of the scalp similar to a serpent forming a turban over the edges of the scalp, and a diffuse form that affects the whole scalp without distinct patches.

See Pathophysiology.