Diagnosis of Acromegaly Patient no 52 A 31 years old female presents with enlargement of the jaw, hands, and feet, which result in increasing shoe and glove size and the need to enlarge finger rings. Her biochemical tests shows: Urea: 6.1 mmol/l (3.5-6.7 mmol/l) Creatinine: 93 μmol/l (50-105 μmol/l) Fasting Plasma Glucose: 16.4 mmol/L (<5.6 mmol/L) a. What is the most likely biochemical diagnosis? b. Name ONE laboratory investigation which can be most helpful in this patient Acromegaly IGF-1 (Glucose suppression test is contraindicated) Ref No 5 Diagnosis of Acromegaly WWW.UpToDate.com

Acromegaly Clinical features of acromegaly are quite typical and are unmistakable. In patients with active acromegaly, the most important first test is IGF-1 If IGF-1 is normal, no further test is required. If IGF-1 is raised or equivocal, Glucose Suppression Test is carried out for confirmation. In scenario, patient has severe hyperglycaemia and glucose suppression test is contraindicated unless glucose level is decreased

Patient no 53 Primordial Dwarfism Yes. There is growth failure A 32 months old boy is being investigated for short stature. He was born prematurely at about 30th weeks' gestation. At birth, he was very small (1.7 kg) and measured 14 inches in length. His growth is fully formed and proportional except some microcephaly. On examination he was found to be < 1st percentile in height and weight. All his routine biochemical, endocrine and immunological tests were normal. He underwent growth studies which revealed: IgF1: Normal for age and sex IgFBP3: Normal for age and sex Growth Hormone (Basal): 4 ng/ml Growth Hormone (after Insulin Stimulation Test): Normal response What is the most probable diagnosis in this patient? Is the ‘Growth Velocity’ low in such patients? Primordial Dwarfism Yes. There is growth failure Ref No 8 Primordial Dwarfism www.primordialdwarfism.com/medmain3.htm

Primordial Dwarfism Common features: Several poorly defined syndromes are grouped together in “Primordial Dwarfism”. Seckle Syndrome is the prototype Common features: Intra-uterine Growth Retardation or Small for Gestational Age is hallmark Severe growth failure persists in post-natal life Height percentile is very low (<3rd percentile) There growth is generally proportional except microcephaly present in many cases Growth Hormone studies are normal Their may be anaemia or pancytopaenia

Primordial Dwarfs (From Abroad)

Primordial Dwarf (Reported in our Department) Patient with our Registrar Patient Age: 9 years Patient with his Father Note: Pictures were taken after permission from father of the patient

Thalassemia and Aberrations of Growth and Puberty Patient no 54 Two children with thalassemia major presented in a Growth Clinic: A 7 years boy with height < 3rd percentile. Lab Tests showed: IGF-1: 15.2 Ug/L (136-385) IGFBP-3: 198 pg/ml (4567 – 8965) Growth Hormone (GH) Stimulation Tests: Normal Response A 13 years girl with height < 3rd percentile. Lab Tests showed: IGF-1: 25.2 (Ug/L (136-385) GH Stimulation Tests: sub-normal Response What are the causes of short stature in these two thalassemic children? Name TWO hormones you will like to test in the girl. 1. GH insensitivity due to IGF defect. 2. GH def due to pituitary defect FSH and LH Ref No 9 Thalassemia and Aberrations of Growth and Puberty ttp://www.mjhid.org/article/view/4612

Short Statured Thalassemic Children IGF-1 axis is affected earlier due to iron deposition So GH insensitivity may be present in these children Later in life iron deposition also starts in pituitary and other endocrine organs causing decrease GH secretion and puberty failure Absence of sex steroid also causes short stature Other factors include malnutrition and Vitamin D def