The Albright syndrome associated with acromegaly and hyperthyroidism (a case report).
The Albright syndrome (fibrous dysplasia) is a clinical entity characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction which in females is associated with precocious puberty. Association of multiple endocrinopathies with Albright syndrome is a rare occurrence, so we thought it worthwhile to report such a case having features of acromegaly and hyperthyroidism.
A 28 year old male patient was admitted because of gradually increasing size and distortion of face and head since 12 years, tremors in hands and feeling of excessive heat with decreased libido for the last 3 years, enlargement of feet, leading to frequent changes of the shoes since 2 years, a gradually increasing painless swelling in the left half of the anterior aspect of the neck for the last 1½ year and acne over the face and back for the last 7 months. Also other noted features were thickness of voice, enlargement of fingers and polyphagia for the last few months.
There was no history of headache, vomiting, diplopia, trauma, fever, sleep disturbances or drug intake.
He was a father of an 8 year old child, and had three brothers and one sister. All family members were well. He weighed 60 kg and had height of 170.5 cm. His blood pressure was 140/70 mm Hg. and pulse 106 minute and regular. Fine tremors, more on stretching out of fingers were present. Face and skull were big, broad and asymmetrical. Acne were present over the face and back. The patient had coarse features, thick and enlarged hands and fee, prognathism, teeth wide apart and a broad nose. One irregular pigmented macule, 2 x 6 cm in size was present over the nape of neck on the right to the midline. One thyroid swelling, left to midline was present. Fundi were normal and so also the fields and acuity of vision.
Investigations revealed normal blood count, urine, stool, skiagram of the chest and electrocardiogram with blood urea-18.5 mg/dl, serum cholesterol-177 mg/dl., blood sugar-139 mg/ dl. Glucose tolerance test after 75 gm of oral glucose load at I hour was 151.0 mg/dl, 1 hr.181 mg/dl, 11/2 hr.-147.0 mg/dl, 2 hr.-139.0 mg/dl., serum creatinine was 1.86 mg/dl, serum sodium-140.0 mEq/L, potassium-4.5 mEq/L, serum proteins-5.9 gm/dl, albumin-3.2 gm/dl, globulin-2.7 gm/dl, serum alkaline phosphatase -48.8 KA units/dl, serum calcium-9.5 mg/dl, phosphorus-3.5 mg/dl, 24 hour urinary 17 ketosteroids-15 mg and 24 hour urinary VMA2.5 mg radioactive 131I uptake was 47.1%, and 54.5% at 4 hours and 24 hours respectively. T3 levels were 3.8 ng/ml, with T4-17.5 µg/dl and TSI3-undetecab!e.
X-ray of the skull showed gross enlargement of the skull, facial bones and mandible, widened, diploic spaces of flat bones with loss of distinction between the inner and outer tables. Occipital protuberance was markedly prominent with areas of increased density in the skull bones. Sella turcica was markedly widened and distorted.
Heel pad thickness on the left was 32 mm and on the right was 30 mm. Soft tissue thickness in all tufts of fingers increased with coarsening of trabeculae of bone. The joint spaces between metacarpo-phalangeal joints and distal interphalangeal joints were widened.
Facilities for CT scan of brain and GH measurements were not available.
A diagnosis of Albright syndrome having bony lesions, characteristic skin pigmentation with acromegaly and hyperthyroidism was made. Symptomatic therapy was given and patient was asked for regular followup.
Albright and his associates, described a syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females. The skeletal lesions affecting one, a few, many or almost every bone in the body are the essential features of this entity and may or may not be accompanied by either or both of the other two features.
The disease does not appear to be hereditory and the frequency is approximately the same in both sexes.
Bony lesions may be mono-ostotic or poly-ostotic or its variant. Mono-ostotic form is the most common and majority of the lesions are located in the craniofacial bones or ribs. Mono-ostotic fibrous dysplasia is most often diagnosed at the age of 20-30 years. The roentgenographic appearance of the lesion is that of a radio-lucent area with a well delineated, smooth or scalloped border, typically associated with focal thinning of the cortex of the bone. Involvement of the facial bone may create a leonine appearance (Leontiasis ossea). The alternating areas of translucency and increased opacity has been stressed by Albright et al as distinctive of fibrous dysplasia. A flat bone may increase 6 to 8 folds or more in thickness. The occipital and frontal bulges and the grossly thickened, dense, hyperostotic base are all characteristic. Serum calcium and phosphorus are usually normal. Serum alkaline phosphatase level is raised in half of the cases of poly-ostotic fibrous dysplasia.
The most frequent extraskeletal manifestation is the skin lesion. The abnormal cutaneous pigmentation consists of isolated dark brown to light brown macules which tend to remain on one side of the midline, the border is usually, although not always, irregular or ragged (coast of Maine) in contrast to the smooth borders of the pigmented macule of neurofibromatosis (coast of California). As a rule, there are fewer than six of the total lesions, which range in size from one cm to those covering very large areas, particularly the back buttocks or sacral regions.
The sexual precocity of unknown cause is found in females and rarely in males., Another endocrine abnormality present with increased frequency is hyperthyroidism. This is always associated with low or undetectable TSH levels and most patients have multinodular goiters rather than the typical findings of Grave's disease. Rare association includes the Cushing's syndrome, hyperparathyroidism,, acromegaly,,,,, possibly hypogonadotrophic hypogonadism and soft tissue myxomas.
Association of multiple endocrinopathies is a rare occurrence, although gigantism and hyperthyroidism in one case of Albright syndrome was recorded by Firat and Stutzman. The etiology of the endocrinopathy is not known but the following opinions prevail: (i)that the endocrinopathies are the result of the hypothalamic hypersecretion of releasing hormones,, and (ii) that the involved endocrine organs are unduly sensitive to trophic hormones or act in an autonomous fashion.
The diagnosis of acromegaly must be made with caution when poly-ostotic fibrous dysplasia is present. Involvement of the facial bones and mandible with fibrous dysplasia can produce gross distortion of the facial features which may be suggestive of acromegaly. The effect of excess growth hormone upon other organ systems besides bone must serve for a diagnostic criterion of acromegaly in the presence of Albright syndrome.
Symptomatic fibrous dysplasia can be managed by a variety of orthopaedic operative procedures such as osteotomy, curettage and bone grafting. Calcitonin may be effective in treatment of wide spread disease associated with bone pain and high serum alkaline phosphatase levels.
The authors are thankful to the Principal and Controller, R.N.T. Medical College and General Hospital Udaipur for his kind permission to publish this case.