Presentation on theme: "Endocrine dysfunction (Hormone imbalances) in Diamond Blackfan Anemia"— Presentation transcript:
1 Endocrine dysfunction (Hormone imbalances) in Diamond Blackfan Anemia Dr Amit LahotiDr Phyllis SpeiserCohen Children’s Medical Center of New YorkNorth Shore LIJ Hospital System
2 Diamond Blackfan Anemia (DBA) is a rare condition.Really!!!
3 DBA Beta thalassemia Sickle-cell disease 5-7 per 1,000,000 live births 1 per 500 African-American live birthsSickle-cell disease
4 Role of a registryFor rare conditions, clear guidelines on how to manage the disease or its complications often not available. A registry provides a unique opportunity to do systematic research. Until more research data are available, doctors use best practices learned from other somewhat similar conditions.
5 Treatment course of DBA BMT recipientsIn a cross-sectional analysis of the DBAR at a given timepoint, 40% of patient are receiving transfusions, 40% are on steroids, and 20% have received a BMT or are in remission.There is a 20% chance of going into remission but not 20% of the patients are in remission at any given time.
6 Pros and cons of DBA treatments CorticosteroidsChronic TransfusionsBone marrow transplantProsNo risk of iron overloadFirst line treatment for severe anemia under 1yCan lead to resolution of anemiaCan improve quality of lifeConsRisk of low bone densityFrequent hospital visits for transfusionsRisk of Graft versus Host Disease (GVHD), and infectionExcess weight gain & impaired growthEndocrine complications of iron overloadRisk of graft rejectionIncreased risk of diabetes (at high doses)Side-effects of immunosuppressive drugs & radiation
7 Where do hormones come from and what do they do?
8 Risk ofHormone disordersin patients with DBA:Is it real?
9 *Unpublished data presented at Pediatric Endocrine society meeting at Washington DC, 2013
10 You or some one sitting next to you may have a similar story…. At 6 months: Diagnosed with DBAMonthly transfusions started.Subsequently developed Iron overloadChelation therapy with Desferal startedAt 14.5 years, 7/2004: went to ER for frequent urination, excessive thirst and 15 lb weight loss. Blood glucose markedly elevated. Diagnosed with Diabetes mellitus,Insulin therapy startedTwo months later, 9/2004: Thyroid function tests show Thyroid gland failure.Thyroid hormone startedDesferal started by nightly subQ pump
11 In the next year…At 15 years, 12/2004: Teen non-compliant with insulin regimen & diet. Poor blood glucose control, stunted growth, despite normal GH levels. Diagnosed Growth hormone resistance.Growth hormone therapy startedAt years, 10/2005: Delayed puberty with evidence of Pituitary failure.Testosterone therapy started.At 16.5 years, 5/2006: Multiple seizures related to low blood glucose despite not being compliant with insulin regime. Diagnosed with Adrenal insufficiencyHydrocortisone therapy started.
12 And as time went by…Two months later, 7/2006: Complaints of frequent urination at night. Diagnosed Diabetes insipidus.DDAVP treatment started.At 17.5 years, 8/2007: Evidence of Diabetic kidney damage.Enalapril treatment started.At 18 years, 2/2008: Growth hormone therapy stopped. Adult height: 5 feet.
13 Hormone problems can start in childhood! You are never “too young” to be tested.Early diagnosis can avoid later problems.
14 Questions?What are these conditions? How common are these? Are you at risk? How can you be tested for these? How are they treated?
15 HypogonadismWhat is it?Absent or delayed puberty
16 Hypogonadism What is Delayed Puberty? In girls, no breast development by 13 years, or no periods by 15 years or by 2 years after breast development.In boys, no testicular enlargement by 14 years
17 Hypogonadism How common? How to diagnose? How to treat? With iron overload: %After BMT:Females- ovarian malfunction in ~100%Males- testicular dysfunction in 0-40%Howcommon?Blood sampling for pituitary puberty-regulating hormones (LH and FSH) andsex hormones (Testosterone or Estradiol). Bone age x-ray of hand.How todiagnose?Males: Testosterone injections or skin gel.Females: Estrogen oral or skin gel.How totreat?
18 Insufficient thyroid hormone HypothyroidismInsufficient thyroid hormoneWhat is it?
19 Hypothyroidism Or, no symptoms at all!!! ( especially in early stages) Feeling coldout of ordinaryHow you may feel?Not growing wellOr, no symptoms at all!!! ( especially in early stages)
20 Hypothyroidism How common? How to diagnose? How to treat? Patients with iron overload: 2-20 %Patients on steroids and after BMT:Less common, frequency unknownHowcommon?By measuring blood levels of:Thyroid stimulating hormone (TSH); andTotal and free Thyroid hormone (T4)How todiagnose?How totreat?Once a day thyroid hormone (tablets)
21 Adrenal insufficiency Not enough adrenal hormonesWhat is it?Stress hormone (cortisol)Salt retaining hormone (Aldosterone)Male hormones
22 Adrenal insufficiency Dark color of non-sun- exposed areasLow BP and dizzinessExtreme tirednessNausea, vomiting, abdominal pain, diarrhea, constipationMuscle weaknessAlthough the picture I have used is of an old lady, not everybody who develops this is oldSymptoms may be missed or attributed to anemia or missed!
23 Adrenal insufficiency Patients on steroids: considered to have adrenal insufficiency Patients with iron overload: biochemical adrenal insufficiency (often partial): 18-45%Howcommon?Blood measurements of:8 AM cortisol level,Plasma renin activity, aldosterone, Androstenedione and DHEAS levelsHow todiagnose?Hydrocortisone: to replace stress hormone.May only be needed during periods of stress.Fludrocortisone: salt-retaining hormone.How totreat?
31 Diabetes mellitus Both iron overload and glucocorticoids lead to: ↓in insulin secretion; and↓ in insulin sensitivity
32 Diabetes mellitus How common? How to diagnose? How to treat? With Iron overload: 9-14%On Chronic glucocorticoids: dose dependent. May be reversible.BMT: depends on pre-transplant factors.Howcommon?Fasting blood glucoseFructosamine level (HbA1c may not bereliable if on transfusions)Oral glucose tolerance testHow todiagnose?Diet changes,Insulin therapy and/orOral medicationsHow totreat?
33 Growth Problems For patients <18 years age: How many of you are shown your/ your child’s growth chart during the visit with the pediatrician or hematologist?How many of you have asked to see your/ your child’s growth chart during these visits?Growth chart is an important tool to detect poor growth or short stature at an early age!!!
35 Growth problems Short stature Anemia and ?DBA itself Absent/ Abnormal pubertyIron overloadShort statureHypothyroidismLow Growth hormoneGlucocorticoidsMultiple causes of poor growth in DBA patients
36 Growth problems How common? How to diagnose? How to treat? DBA itself: Reported short stature ~30%Effect on growth due to iron overload orsteroids alone is hard to quantify inDBA due to this.BMT: may improve growth.Howcommon?Regular growth monitoring for earlydetectionLaboratory testing to rule out specificendocrine causes.How todiagnose?When to treat?Specific to the cause.However, final height may still be low formid-parental height.How totreat?
38 Bone disorders Weak bones Hypogonadism Low Vitamin D & parathyroid gland failureIron overloadWeak bonesDiabetes mellitus? Low Growth hormoneGlucocorticoidsMultiple causes of poor bone density in DBA patients
39 Bone disorders How common? How to diagnose? How to treat? With Iron overload: upto 50%On Chronic glucocorticoids: Dose and duration dependent.After Bone marrow transplant: Not knownHowcommon?Test for other endocrine problemsBlood levels of Calcium, parathyroidhormone and vitamin DBone mineral density scanHow todiagnose?When to treat?Treat any co-existing hormone problemVitamin D supplements: Adequate level?Other medications: BisphosphonatesNewer drugs being developed.How totreat?
40 Importance of Screening Vague symptoms may also be seen with anemia itself.Often no/minimal symptoms in early stages.14%impaired glucose tolerance1.5%Diabetes mellitus84.5%: normalDiabetes screening in non- diabetic otherwise asymptomatic beta thalassemia patients
42 Importance of Chelation Impaired glucose tolerance (IGT)Years12.4%Normal glucose tolerance~10 YearsInsulin dependent diabetes mellitusIntensive chelation in patients with IGT can improve beta-cell function, improve blood glucose values.Less effective in patients who have developed DM and in improving insulin resistance.
43 Treatable nature of most of these conditions Treatable nature of most of these conditions!- That’s what I love about endocrinology!!!Timely diagnosis & treatment can prevent morbidity and possible mortality associated with some endocrine conditions.Versus possible long-term adverse effects of an untreated endocrine problem.
44 What do we need to do?The only published reports about hormone problems in DBA patients are in form of case reports or case series with few patients.Collect more information about endocrine problems in DBA patients like you.Vs
45 About our research study SPECIFIC AIMS:To study the effects of iron overload on various endocrine glands in DBA patients receiving transfusions.To estimate how common are these hormone abnormalities in the DBA population and correlate it with measures of iron overload.To recommend a possible method to screen the at-risk DBA patients for endocrine dysfunctions at regular intervals.To compare the presence of endocrine dysfunction in chronic transfusion dependent DBA population with DBA patients not on chronic transfusions and beta thalassemia major patients on chronic blood transfusions.
46 About our research study Eligibility Criteria:Inclusion criteria:Age 1-39 years; andDiagnosed with DBA and enrolled in DBA Registry (DBAR), orDiagnosed with beta thalassemia major and followed at NSLIJ pediatric hematology division.Exclusion criteria:Pregnant; orHaving received a bone marrow transplant
47 About our research study Participation involves a standard endocrine evaluation.This includes blood tests that can be ordered and drawn atyour primary institution. The participation consent asks forpermission for us to receive the endocrine evaluation results.Our goal is 75 DBA patients and 25 thalassemia patients total for the study. THANK YOU IN ADVANCE FOR YOUR PARTICIPATION!!!