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BY DR. OM LAKHANI , MD
IMPORTANT POINTS These notes are made from Standard Textbook of Medicine The Yellow shades refer to things you have to revise frequently (atleast once a week) The Blue shades refers to concepts The Pink shades refers to concepts that are not required for undergraduate level but useful for Postgraduate level.
Q. Define acromegaly Acromegaly is a condition of increase growth hormone levels. It is associated with other comorbities and increase mortality as compared to general population. It is because of pituitary macroadenoma in more than 70% cases. (Katznelson et al., 2011)
Q. What is the prevalence of acromegaly ? Acromegaly is rare is rare condition. It is present in 40-125 per million population. It is generally diagnosed in mid 40s. It is associated present equally in males and females Q. Which is the most common cause of Acromegaly ? Acromegaly is most commonly due to GH Secreting Pituitary adenoma (Somatotrope adenoma) Q. Which tumors produce both GH and Prolactin ? Mammosomatotroph adenoma Acidophilic adenoma- Prolactin is more predominant Q. Can excess of GHRH secretion cause Acromegaly ? GHRH is produced by Hypothalamus Yes GHRH secreting tumors can classical present as Acromegaly It is classically produced ectopically by Bronchial Carcinoids © DR. OM LAKHANI, WWW.MEDICINENOTES.IN Page 1
large fleshy nose etc. Which are the other endocrine disorders associated with acromegaly ? Acromegaly is associated with 1. © DR. Features of Hyperprolactinemia a. There is a risk of Cardiovascular complications and acromegaly is associated with increase insulin resistance. Type 2 Diabetes mellitus. Males.often central hypothyroidism (Low TSH and T4) 3. OM LAKHANI. arthralgias. WWW. patient could have acral enlargement. Acromegly is an important cause of osteoarthritis and carpal tunnel syndrome. Obstructive sleep apnea is also commonly seen. Cardiovascular features including hypertension is seen in 30% cases. What are the other features of acromegaly ? As a consequence of Increase growth hormone. Excessive sweating. testosterone deficiency 2. Important signs include increase Heel Pad thickness.MEDICINENOTES. low self esteem etc.Amneorrhea. Q. Visual field defects are often associated.IN) Rarely it may be produced by Hypothalamic tumors CLINICAL FEATURES OF ACROMEGALY Q. fatigue and weight gain. Acromegalic cardiomyopathy. It is an important cause of sleep apnea. Hypothyroidism. Which is the most common clinical presentation of acromegaly in women ? Amenorrhea is the most common complaint in women Q. maxillofacial swelling .ENDOCRINOLOGY (WWW. How common is diabetes in acromegaly ? 25% cases of Acromegaly develop diabetes Q. Often associated with multinodular goitre 4.IN Page 2 . 4-14% of those have hyperthyroidism. It may also be associated with psychological alterations like body image disruption. Females .hypogonadism. increasing shoe size . associated with biventricular enlargement is hallmark of acromegaly. galactorrhea b.MEDICINENOTES.associated in 73% cases. Thyroid nodules. Headache is the most common complaint of tumor enlargement.
ENDOCRINOLOGY (WWW. What are the pitfall associated with IGF -1 measurement ? IGF-1 can be false positive in pregnancy. Q. However.MEDICINENOTES. Which are other tests similar to IGF-1 that are used for acromegaly ? Insulin like growth factor binding protein 3 (IGFBP 3) and acid labile unit (ALS) are other markers that can be used. Do these patients have a higher risk of cancer ? Association of acromegaly with colon cancer is known. Q. Q. If IGF-1 level is elevated in a patient with symptoms of acromegaly. Cause of false negative IGF-1 include Renal failure Liver failure Uncontrolled diabetes mellitus Malnutrition OC pill use Q.to measure GH suppression 3. WWW. OGTT may be omitted for diagnosis.IN) Q. Oral glucose tolerance test. Free IGF-1 and IGF binding protein are not required for diagnosis. OM LAKHANI. their use is not validated and IGF-1 is considered a better marker. Why not measure GH directly ? GH is secreted in a pulsatile fashion and hence measurement of GH secretion is not clinically useful in acromegaly. MRI pituitary – look for pituitary tumor Q. DIAGNOSIS OF ACROMEGALY Q. Which are three important tests for diagnosis of acromegaly Three important tests include 1.IN Page 3 . What is the importance of measurement of IGF-1 ? IGF-1 serves an excellent screening test for acromegaly. Measurement of IGF-1 2. How is OGTT for GH done and what is its interpretation ? © DR.MEDICINENOTES.
What should be done if MRI pituitary is normal. Any value of GH <1 ng/ml is considered normal. GH receptor antagonist (Pergvisomant) c. surgical debulking is still advised. What are the treatment options in patients with acromegaly ? Three are three treatment options in acromegaly 1. any value of 0. Radiation therapy Q. Q.IN Page 4 . OM LAKHANI.MEDICINENOTES. This is especially for microadenomas and macroadenomas with mass effect. Q.4 ng/ml is now considered by AACE as normal.ENDOCRINOLOGY (WWW.IN) To look for GH suppression using OGTT patient is given glucose load and the GH is measured every 30 min for 3 hours. What do you except after surgery ? © DR. CT scan or octeroscan may be done to locate the tumor. WWW.MEDICINENOTES. Surgical therapy 2. Q. Dopamine agonist (Carbergoline / Bromocriptine) 3. However. Somatostain analogues (Octerotide) b. Giving glucose should suppress Growth hormone. What is the cure rate after surgery ? Microadenomas has a cure rate of 70% after surgery Macroadenomas have a cure rate of <50% after surgery Risk of Recurrence is 10% Risk of Hypopituitarism is 15% Q. because of increased sensitivity of GH assays. Medical therapy a. What is the primary mode of treatment in acromegaly ? The primary mode of therapy is surgery. If Growth hormone fails to suppress it is considered marker of Acromegaly. In those microadenomas without mass effect and tumors unlikely to be cured by surgery. yet patient has features of acromegaly ? In such a case diagnosis of ectopic GH secreation must be considered. Q. Which are the other tests done for acromegaly ? Prolactin and TSH /T4 measurement must be done in patients with acromegaly as they are often associated with acromegaly. Bronchial carcinoid often secreate GHRH and GH. TREATMENT OF ACROMEGALY. MRI pituitary is done to locate the tumor and confirm its size.
What is the role of other therapies in management of acromegaly ? Medical therapy is generally used as adjuvant therapy. Radiotherapy is generally used as adjuvant therapy. OM LAKHANI. Give an algorithm for management of acromegaly (simplified) ACROMEGLY Surgery Feasible Not feasible Surgery SSA or DA GH/IGF1 controlledMONITOR GH/IGF1 not controlled. WWW.IN) Soft tissue swelling reduces immediately after surgery GH levels reduce within 1 hr IGF-1 levels reduce within 3-4 days Q.ENDOCRINOLOGY (WWW.Somatostain analogue.MEDICINENOTES.MEDICINENOTES. Medical therapy may be used as primary therapy in patients who are unlikely to respond to surgical therapy.dopamine agonist MEDICAL THERAPY FOR ACROMEGALY © DR.Debulking Surgery Surgery Not feasiblePERGVISOMANT / RADIOTHERAPY SSA.SSA /DA GH/IGF1 controlledMONITOR GH/IGF1 not controlledincrease dose of SSA /DA Not controlled PERGVISOMANT Surgery Feasible now.IN Page 5 . Q. DA.
IGF1 and Prolactin measurement 4-6 week after dose challenge is used for monitoring efficacy. Persistently non suppressible GH or elevated IGF-1 after pituitary surgery 2. Octerotide is used in dose of 50ug sc three times a day before switching to long acting octreotide LAR to assess toxicity and response to therapy. In which case is medical therapy used as adjuvant therapy ? As adjuvant therapy it is used in 1. Low likelihood for surgical remission.50 ug and 100 ug) : Short acting octreotide also used before starting long acting agents. Poor surgical candidates 3. OM LAKHANI.IN) Q.MEDICINENOTES. WWW. Value <1 ng/ml is suggestive of efficacy For Pegvisomant therapy . What is the role of Dopamine agonist in acromegaly ? Dopamine agonist have some role in management of acromegaly This is especially true for those patients who have co-secretion of prolactin and lesser IGF1 elevation Higher dose of Cabergoline is however required in this case as compared to Prolactinoma Repeat GH. How do you biochemically monitor medical therapy ? GH levels (after OGTT) are measured to monitor therapy. In which cases would you use primary medical therapy for acromegaly ? Primary medical therapy is preferred for patients with 1. Q.ENDOCRINOLOGY (WWW.Macroadenoma with cavernous sinus invasion 2.MEDICINENOTES. Patient preference Q. Interim period after RT Q. Q. IGF1 is used for monitoring as GH levels actually increase.IN Page 6 . Which are the various Somatostatin analogues used in treatment of acromegaly and what is the dosing ? Short acting Octreotide (Sandostatin. What is the mechanism of action of Somatostatin analogues (SSA) in Acromegaly ? SSA exerts its action on GH adenoma through SSTR2 and SSTR5 both of which are present in GH adenoma Q. © DR.
IN) Long acting. WWW. then the dose may be modified based upon response. What are the ADRs of Pegvisomant ? Local lipohypertrophy Flu like effect Increase in transaminases (transient) Q. Q. Does GH level reduce after Pegvisomant therapy ? No. Q.MEDICINENOTES.ENDOCRINOLOGY (WWW. It is given in Dose of 10-20 mg sc daily Q.MEDICINENOTES.M. intragluteally every 4-6 weeks for 3 months. OM LAKHANI. What is PEGVISOMANT ? Pegvisomant is a highly selective GH antagonist used in treatment of acromegaly. Pegvisomant can cause fall in IGF-1 but not in GH levels. What is the advantage of Pegvisomant in diabetics ? Pegvisomant is found to improve glucose homeostasis and hence can be preferred over SSA in diabetic patients. Q. What are the benefits of SSA ? Headache and soft tissue swelling reduces within days to weeks in 75% cases Tumor size reduces in 40% cases but there is relapse after stopping therapy Even after 20 years of Use tolerance to therapy doesn’t occur. GH levels may actually increase © DR. LANEROTIDE 30 mg IM injection every 2 weeks. What are the side effects of SSA ? Abdominal cramps are most common side effect They can increase risk of Gall stone formation because of Reduce gall bladder contractility There is potential risk of developing diabetes mellitus or worsening of sugar control in diabetics Q.IN Page 7 .Octreotide LAR (Sandostatin LAR) 30 mg I.
Fall in both IGF-1 and GH Pegvisomant.MEDICINENOTES. Radiotherapy cannot cause a fall in IGF-1 Pearl SSA and Surgery. true gigantism is because of actual GH secreting tumor which is less common.Fall in GH .IN Page 8 .MEDICINENOTES. Cyberknife and linear accelerator. WWW. no fall in GH Radiation. Q. no fall in IGF1 PITUITARY GIGANTISM Q. Q. What is the role of radiation therapy in acromegaly ? Radiation therapy is mainly used as adjuvant therapy . What are the types of Radiation therapy? Radiation therapy are of two types Conventional fractionated Radiotherapy.. What is the biggest hurdle with RT treatment ? The biggest hurdle with RT treatment is development of Hypopitutarism which occurs in 50% of patients over 5-10 years Apart from this RT carries a potential threat to eyesight and risk of Cerebrovascular accident. What is true pituitary gigantism ? Gigantism can be because of both hypogonadotrophic hypogonadism (more common) as well as GH secreting adenoma (less common) in children before closure of epiphysis.ENDOCRINOLOGY (WWW. Q.given in dose of 160-180 cGy .Fall in IGF1 . 4-5 days a week for 4-6 weeks period Sterotactic Radiosurgery – Includes Gamma knife. Q. However. What are the features of Pituitary gigantism ? Increased linear growth with mild obesity © DR. Do you except IGF1 to fall after Radiotherapy ? No. It can reduce the size of tumor but has little biochemical advantage.IN) RADIATION THERAPY Q. OM LAKHANI.
MEDICINENOTES. WWW.ENDOCRINOLOGY (WWW. © DR. The mutation causes defect in G protein which keeps the adenyl cyclase in constantly activated form These patients have polyostotic fibrous dysplasia which may be unilateral Café – au luit spots which too may be unilateral and have been described as ‘Coast of Maine’ appearance Precarious puberty especially in girls in whom menstrual cycles may start as early as two years of age GH excess leading to acromegaly Sometimes associated Cushing’s syndrome Treatment of GH excess in McCune Albright is predominantly medical management. What is McCune Albright syndrome and how does its management differ from acromegaly ? McCune Albright syndrome occurs because of mutation in GNAS gene.IN Page 9 . Surgical and radiation therapy is not employed as there is alerted bony anatomy as a result of the fibrous dysplasia. however such therapy is not contraindicated and may be justified in selected cases as add on therapy to somtastain analogues.MEDICINENOTES. OM LAKHANI. GH receptor antagonist are not tried much in management of McCune Albright. Medical management is generally with Somatostatin analogues with or without Dopamine agonist.IN) Macrocephaly in children Visual field compromise Oligomenorrhea or amenorrhea in girls OTHER POINTS Q.
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