mccune albright syndrome is rare with an estimated prevalence of 1 in 100,000 to 1 in 1,000,000 persons .
the classical clinical triad consists of fibrous dysplasia of the bone , caf - au - lait skin spots and precocious puberty .
she had a short stature , round face , thick neck , and short fourth metacarpals and metatarsals .
serum calcium , phosphorus and parathyroid concentrations were normal , but gonadotropin hormones were very low .
x - ray examination revealed short fourth and fifth metacarpals , short left metatarsal , and short fibula .
these local bony abnormalities along with the biochemical findings helped us to diagnose this case as an unusual presentation of primary hypogonadism with features of mccune albright s syndrome where there was amenorrhea rather than preocious puberty .
it is commonly seen in patients with albright s hereditary osteodystrophy ( aho ) which is a constellation of physical features that include short adult stature , obesity , brachydactyly , and ectopic ossifications .
aho patients who have normal end - organ responses to parathyroid hormone ( pth ) constitute the rare disorder pseudopseudohypoparathyroidism ( pphp ) .
a short fourth metacarpal is seen in approximately 65% of such patients ( 2 ) .
this is distinct from pseudopseudohypoparathyroidism ( pphp ) which presents with hypocalcemia , hyperphosphatemia , and high levels of parathyroid hormone ( pth ) .
it is associated with a possible resistance toward several hormones such as thyroid stimulating hormone ( tsh ) , luteinizing hormone ( lh ) , follicle stimulating hormone ( fsh ) , growth hormone releasing hormone ( ghrh ) that mediate their action through the g - protein - coupled receptors ( 3 ) .
an eighteen - year old female with height of 138 cm and weight of 66 kg was referred to the endocrine department of a multispecialty hospital of eastern india , in mid 2015 .
however , the reported menarche was actually an episode of induced bleeding due to an unknown medication provided by a local doctor .
born to nonconsanguineous parents , the patient was an unmarried college student who reported to be apparently healthy with no significant past history .
there was no complaint of symptoms such as cramping , tetany , twitching , or seizure .
there was no history of thyroid or other surgery , radiation or any systemic illness .
her blood pressure was 100/60 mmhg , temperature 37c , pulse rate 78 min and respiratory rate 20 min .
physical examination revealed breast bud formation with a small area of surrounding glandular tissue and areola beginning to widen .
the fourth and fifth metacarpals on both sides were short with the knuckles being depressed in the clenched fist position ( figure 1 ) .
chvostek s sign , trousseau s sign , and signs of neuromuscular irritability were negative .
depressed 4th and 5th finger knuckles in the clenching fist position when a family history was sought , the patient revealed she felt that her grandmother had the same general physical features of short height , round face , thick neck and particularly the appearance of her hands and feet .
x ray of the skull ( figure 3 ) revealed normal appearance of the pituitary fossa .
shortening of metacarpals iv and v x ray of the skull showing normal pituitary fossa reports from tests done six months back in an outside laboratory revealed lh 0.8 miu / ml ( 1.58 ) , fsh 2 miu / ml ( 312 ) , prolactin 4.1 ng / ml ( 535 ) , and dehydroepiandrosterone sulphate ( dheas ) 0.79 g / dl ( 25.9460.2 ) . at presentation to our hospital , laboratory investigations were repeated . the fasting plasma glucose , serum calcium , phosphorus and alkaline phosphatase , blood urea , blood creatinine , serum 25 hydroxy vitamin d , serum magnesium , 24 hr urinary calcium , parathormone ( pth ) , tsh , growth hormone ( gh ) , insulin- like growth factor 1 ( igf-1 ) levels and erythrocyte sedimentation rate ( esr ) were within the reference ranges .
nmol / l ( > 300 ) , estradiol < 9 pg / ml ( 18575 ) , and fsh 1.63 miu / ml ( 312 ) .
chromosomal karyotyping revealed normal female karyotype ( 46xx ) with no numerical or structural chromosomal anomalies at 450550 banding resolution .
due to financial constraints of the patient , mri of the hypophysis , though advised , could not be done .
molecular genetic testing done at another laboratory outside the hospital identified a mutation in the gnas gene .
this case has the classic findings of albright s facies with short fourth metacarpals and metatarsals , normal serum calcium , phosphate and pth levels diagnostic of pseudopseudohypoparathyroidism with an added unusual feature of hypogonadism .
( 4 ) described the metacarpal sign ( shortening of the fourth and fifth digits , presenting as dimpling over the knuckles of a clenched fist ) as a diagnostic marker of gonadal dysgenesis . in males , this metacarpal sign occurs much more frequently in the presence of some gonadal anomaly than when the gonads are normal .
patients showing the metacarpal sign usually have delayed skeletal development , reflected as short height and short fourth and fifth metacarpals .
this deformity is seen more often in females and is hereditary in nature ( 5 ) .
short fourth and fifth metacarpals and metatarsals are seen in pseudo - pseudohypoparathyroidism , gonadal dysgenesis ( turner s syndrome / chromosomal disorder 45xo ) , pseudohypoparathyroidism and familial brachydactylism , with hypogonadism being associated with the first two conditions ( 6 ) .
trauma is the most common cause of this deformity but other causes include neurofibromatosis , congenital adrenal hyperplasia due to 11 beta hydroxylase deficiency , ( 5 ) familial short stature , hereditary multiple exostoses , patients with homocystinuria and other less common syndromes ( 8) . an alteration in the coding sequence of the gnas gene leads to a haplo - insufficiency and a dysmorphic phenotype referred to as albright s syndrome or albright s hereditary osteodystrophy ( aho ) .
it is a clinical syndrome defined by specific physical features that include short stature , obesity , round - shaped face , subcutaneous ossifications and brachytherapy mainly of the fourth and fifth metacarpals .
patients with mutations on their maternally derived allele are likely to have associated phpia , whereas mutations on the paternal allele usually cause pphp .
isolated pth resistance ( phpib ) can result from mutations within the gnas1 gene but is more commonly caused by epigenetic imprinting abnormalities affecting the upstream exon 1a ( 9 ) . in php , there is a hormonal resistance to pth at the kidney level and to tsh at the thyroid level while in pphp , there are few clinical signs with no hormonal resistance ( 10 ) .
however , according to a recent publication , pth and other hormone resistance may be seen in both disorders ( 11 ) .
the characteristic physical features of short stature , round face , brachydactyly of the fourth and fifth metacarpals and the biochemical findings of normal serum calcium , phosphorus and parathyroid hormone concentrations along with a very low level of gonadotropin hormones led us to the diagnosis of albright s syndrome in this patient who presented to us with primary amenorrhea and hypogonadism .
 background : mccune albright syndrome is rare with an estimated prevalence of 1 in 100,000 to 1 in 1,000,000 persons . 
 the classical clinical triad consists of fibrous dysplasia of the bone , caf - au - lait skin spots and precocious puberty . 
 however , in rare cases , there may be primary hypogonadism and amenorrhea.case presentation : an eighteen - year - old female presented with amenorrhea . 
 she had a short stature , round face , thick neck , and short fourth metacarpals and metatarsals . 
 the secondary sexual characters were absent . 
 serum calcium , phosphorus and parathyroid concentrations were normal , but gonadotropin hormones were very low . 
 x - ray examination revealed short fourth and fifth metacarpals , short left metatarsal , and short fibula.conclusion:these local bony abnormalities along with the biochemical findings helped us to diagnose this case as an unusual presentation of primary hypogonadism with features of mccune albright s syndrome where there was amenorrhea rather than preocious puberty . 